bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corydalis yanhusuo W.T. Wang Extract Inhibits MCF-7 Cell Proliferation by Inducing Cell Cycle G2/M Arrest
Authors: Xu Zengtao , Chen Xiuping , Zhang Qingwen , Chen Lidian , Wang Yitao 
Published: May 2011

Corydalis yanhusuo W.T. Wang (YHS) is a traditional Chinese herb widely prescribed for promoting blood circulation, reinforcing vital energy and alleviating pain. Our previous studies showed that an ethanol extract of YHS inhibits metastasis of breast cancer cells in vitro. In the present study, the anti-proliferative effect of the extract was determined by MTT assay and the LDH release was measured with a commercial kit. Intracellular reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) were monitored by CM- H2DCF-DA and JC-1 staining, respectively. Cell cycle was analyzed with propidium iodide (PI) staining by flow cytometry and protein expressions were measured by Western blotting. The YHS extract significantly inhibited MCF-7 cell proliferation in a dose-dependent manner. Significant increase of ROS formation and decrease of ΔΨm were observed. Furthermore, it induced MCF-7 cell cycle arrest at the G2/M phases. In addition, the p-cdc-2/cdc-2 protein expression ratio was increased while Rb and p21 protein expressions were decreased. The YHS extract inhibited MCF-7 proliferation by inducing G2/M cell cycle arrest, which might be mediated by inducing ROS formation, decreasing ΔΨm and regulating cell cycle related protein expressions.
Rethinking weathering and pedogenesis in alpine periglacial regions: some Scandinavian evidence
Authors: Thorn C. E. , Darmody R. G. , Dixon J. C. 
Published: May 2011

Abstract

Research in the Arctic and alpine regions of NW Sweden and south-central Norway reveals an active chemical-weathering regime: in Kärkevagge, Swedish Lapland, pyrite weathers to produce an acidic environment with vigorous chemical weathering and active pedogenesis as indicated by locally well-developed Spodosols; in the Jotunheimen Mountains of Norway, soil horizons form slowly but cobbles develop weathering rinds within
c
. 250 years. Such results indicate that chemical weathering and pedogenesis may be quite advanced in alpine periglacial regions and is just one illustration that such regions may be profitably scrutinized using geomorphological and pedological conceptual frameworks other than the traditional periglacial framework.
Role of lichens in granite weathering in cold and arid environments of continental Antarctica
Authors: Guglielmin Mauro , Favero-Longo Sergio E. , Cannone Nicoletta , Piervittori Rosanna , Strini Andrea 
Published: May 2011

Abstract
The mechanical and chemical effects of lichens on the outer and inner surfaces of tafoni features were investigated through a multidisciplinary approach at two locations (Oasi 74°42′S, 164°07′E, 40–250 m a.s.l.; Mount Keinath, 74°32′S; 163°58′E; 850 m a.s.l.) close to the Italian Antarctic station (Mario Zucchelli). Outer tafoni roof surfaces show low values of effective porosity coupled with pervasive hyphal penetration and an extensive reddish-brown weathering rind. Inner tafoni surfaces show higher values of effective porosity, which correspond with an almost absent weathering rind and low hyphal penetration. Our observations indicate that: (a) iron oxy-hydroxides, particularly concentrated where hyphal patches and bundles contact biotite, consist of hematite; (b) the microcosms of lichen hyphae and their precipitates fill voids to form case hardening on outer surfaces; and (c) on inner surfaces biological action is less active, most likely because of more intense thermal stress and salt action.
Periglacial sediments: do they exist?
Authors: Vandenberghe Jef 
Published: May 2011

Abstract
‘Periglacial deposits’ have often been reported in the Quaternary geological literature. Sometimes their identity has been confused with the periglacial processes, landforms and environments with which these deposits are linked. However, the question arises: what are the diagnostic characteristics of such ‘periglacial’ deposits? A number of examples illustrate that ‘periglacial deposition’ follows the general geomorphological and sedimentological laws, although it may be influenced by specific conditions of vegetation and sediment availability. These may be completely or partly dependent on periglacial climatic conditions. Some marginal conditions are specific to cold environments, for instance the scarcity of vegetation that has a clear effect on transport and deposition of aeolian sediments. In addition, the intensity of some processes is governed by climate-derived conditions, for instance in the case of fluvial and slope processes. In this sense, the answer to the question in the title is negative. ‘Periglacial deposits’ do not correspond to any particular sedimentary process. This conclusion is, however, only valid when post-depositional weathering and deformations at micro- and macro-scale are excluded.
Holocene slope dynamics in Sierra Nevada (south Spain). Sedimentological analysis of solifluction landforms and lake deposits
Authors: Oliva M. , Ortiz A. Gómez 
Published: May 2011

Abstract
The activity of geomorphic processes in the current periglacial belt of Sierra Nevada during the Holocene has been strongly controlled by climate variability. We examined two sedimentary records showing several cycles with varying intensity of slope processes in the massif. Chronostratigraphic studies of solifluction landforms have revealed seven cycles of enhanced slope activity in Sierra Nevada during the last 7 ka. Lake sediments show eight periods with increased slope activity over the last 6 ka. Depending on temperature and moisture regime, erosion or conditions of slope stability prevailed. Cold and wet periods triggered slope processes and favoured deposition of coarse-grained sediments into the lakes, whereas warm phases were prone to soil development and fine-grained sedimentation in the lakes. The lake sediments also show evidence for an increasing aridity trend since the Holocene Optimum Warm Period in Sierra Nevada, which induced a shift of solifluction processes to higher elevations accompanying late-lying snow patches.
Aeolian processes and features in cool climates
Authors: Brookfield Michael E. 
Published: May 2011

Abstract
This review concentrates on the characteristics of wind processes and products in cold lowland deserts. Its main aims are: to show how difficult it can be to separate wind-generated from water-generated processes and features without detailed study of lamination types; to suggest cold aeolian interpretations for some ancient pre-Quaternary rocks; and to encourage students to revisit many ancient deposits with such interpretations in mind. Although upper Quaternary and Recent cold-climate aeolian deposits have been studied for many years there are very few older examples described. Martian features are included since Mars is now one of the most exciting areas of study for geologists.
Palaeoshorelines of glacial Lake Kuray–Chuja, south-central Siberia: form, sediments and process
Authors: Carling P. A. , Knaapen M. , Borodavko P. , Herget J. , Koptev I. , Huggenberger P. , Parnachev S. 
Published: May 2011

Abstract

Glacial lake Kuray–Chuja which occupied the Kuray and Chuja Basins during the Quaternary Period (Marine Isotope Stages 2 and 3) left distinct shoreline features around the basin margins. At the greatest extent the lake had a surface area of 2951 km
2
with wind fetches up to 70 km. Wind waves constructed erosional, erosional-accumulative and accumulative strandlines, the latter including spits, tombolos, barrier beaches and offshore bars. Strandlines range in altitude between
c
. 1600 and 2100 m, the range in altitudes demonstrating lake level variations through time. The shoreline forms and stratigraphy are detailed. Particular attention is given to the presence of pocket beaches on rock-coasts, the alluvial strandlines of which have distinctive alongshore gradients. Although reasonably ascribed to regional differential tectonic uplift, the possibility that the local alongshore gradients are augmented as a process response to alongshore drift of sediment in a sediment-starved system of closed coastal cells is explored using a simple numerical model.
Splicing Factor hnRNP A2/B1 Regulates Tumor Suppressor Gene Splicing and Is an Oncogenic Driver in Glioblastoma
Authors: Golan-Gerstl Regina , Cohen Michal , Shilo Asaf , Suh Sung-Suk , Bakàcs Arianna , Coppola Luigi , Karni Rotem 
Published: May 2011

AbstractThe process of alternative splicing is widely misregulated in cancer, but the contribution of splicing regulators to cancer development is largely unknown. In this study, we found that the splicing factor hnRNP A2/B1 is overexpressed in glioblastomas and is correlated with poor prognosis. Conversely, patients who harbor deletions of the HNRNPA2B1 gene show better prognosis than average. Knockdown of hnRNP A2/B1 in glioblastoma cells inhibited tumor formation in mice. In contrast, overexpression of hnRNP A2/B1 in immortal cells led to malignant transformation, suggesting that HNRNPA2B1 is a putative proto-oncogene. We then identified several tumor suppressors and oncogenes that are regulated by HNRNPA2B1, among them are c-FLIP, BIN1, and WWOX, and the proto-oncogene RON. Knockdown of RON inhibited hnRNP A2/B1 mediated transformation, which implied that RON is one of the mediators of HNRNPA2B1 oncogenic activity. Together, our results indicate that HNRNPA2B1 is a novel oncogene in glioblastoma and a potential new target for glioblastoma therapy. Cancer Res; 71(13); 4464–72. ©2011 AACR.
Imaging DNA Damage In Vivo Using γH2AX-Targeted Immunoconjugates
Authors: Cornelissen Bart , Kersemans Veerle , Darbar Sonali , Thompson James , Shah Ketan , Sleeth Kate , Hill Mark A. , Vallis Katherine A. 
Published: May 2011

Abstract
DNA damage responses (DDR) occur during oncogenesis and therapeutic responses to DNA damaging cytotoxic drugs. Thus, a real-time method to image DNA damage in vivo would be useful to diagnose cancer and monitor its treatment. Toward this end, we have developed fluorophore- and radioisotope-labeled immunoconjugates to target a DDR signaling protein, phosphorylated histone H2A variant H2AX (γH2AX), which forms foci at sites of DNA double-strand breaks. Anti-γH2AX antibodies were modified by the addition of diethylenetriaminepentaacetic acid (DTPA) to allow 111In labeling or the fluorophore Cy3. The cell-penetrating peptide Tat (GRKKRRQRRRPPQGYG) was also added to the immunoconjugate to aid nuclear translocation. In irradiated breast cancer cells, confocal microscopy confirmed the expected colocalization of anti-γH2AX-Tat with γH2AX foci. In comparison with nonspecific antibody conjugates, 111In-anti-γH2AX-Tat was retained longer in cells. Anti-γH2AX-Tat probes were also used to track in vivo DNA damage, using a mouse xenograft model of human breast cancer. After local X-ray irradiation or bleomycin treatment, the anti-γH2AX-Tat probes produced fluorescent and single photon emission computed tomography signals in the tumors that were proportionate to the delivered radiation dose and the amount of γH2AX present. Taken together, our findings establish the use of radioimmunoconjugates that target γH2AX as a noninvasive imaging method to monitor DNA damage, with many potential applications in preclinical and clinical settings. Cancer Res; 71(13); 4539–49. ©2011 AACR.
MicroRNA Sequence and Expression Analysis in Breast Tumors by Deep Sequencing
Authors: Farazi Thalia A. , Horlings Hugo M. , ten Hoeve Jelle J. , Mihailovic Aleksandra , Halfwerk Hans , Morozov Pavel , Brown Miguel , Hafner Markus , Reyal Fabien , van Kouwenhove Marieke , Kreike Bas , Sie Daoud , Hovestadt Volker , Wessels Lodewyk F.A. , van de Vijver Marc J. , Tuschl Thomas 
Published: May 2011

Abstract
MicroRNAs (miRNA) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 noninvasive, 151 invasive breast carcinomas, and 6 cell lines by in-house–developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed sequence–dependent miRNA target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most noninvasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including miR-98/let-7), with most miRNA changes apparent already in the noninvasive carcinomas. In addition, patients that went on to develop metastasis showed increased expression of mir-423, and triple-negative breast carcinomas were most distinct from other tumor subtypes due to upregulation of the mir∼17–92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested. Cancer Res; 71(13); 4443–53. ©2011 AACR.
STAT3 Plays a Critical Role in KRAS-Induced Pancreatic Tumorigenesis
Authors: Corcoran Ryan B. , Contino Gianmarco , Deshpande Vikram , Tzatsos Alexandros , Conrad Claudius , Benes Cyril H. , Levy David E. , Settleman Jeffrey , Engelman Jeffrey A. , Bardeesy Nabeel 
Published: May 2011

Abstract
The STAT3 transcription factor is an important regulator of stem cell self-renewal, cancer cell survival, and inflammation. In the pancreas, STAT3 is dispensable for normal development, whereas the majority of pancreatic ductal adenocarcinomas (PDAC) show constitutive activation of STAT3, suggesting its potential as a therapeutic target in this cancer. Here, we sought to define the mechanisms of STAT3 activation and its functional importance in PDAC pathogenesis. Large-scale screening of cancer cell lines with a JAK2 inhibitor that blocks STAT3 function revealed a more than 30-fold range in sensitivity in PDAC, and showed a close correlation of sensitivity with levels of tyrosine-phosphorylated STAT3 and of the gp130 receptor, an upstream signaling component. Correspondingly, upregulation of the IL6/LIF-gp130 pathway accounted for the strong STAT3 activation in PDAC subsets. To define functions of STAT3 in vivo, we developed mouse models that test the impact of conditional inactivation of STAT3 in KRAS-driven PDAC. We showed that STAT3 is required for the development of the earliest premalignant pancreatic lesions, acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Moreover, acute STAT3 inactivation blocked PDAC initiation in a second in vivo model. Our results show that STAT3 has critical roles throughout the course of PDAC pathogenesis, supporting the development of therapeutic approaches targeting this pathway. Moreover, our work suggests that gp130 and phospho-STAT3 expression may be effective biomarkers for predicting response to JAK2 inhibitors. Cancer Res; 71(14); 5020–9. ©2011 AACR.
Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes
Authors: Pollack Brian P. , Sapkota Bishu , Cartee Todd V. 
Published: May 2011

Abstract
Purpose: Diverse immune-related effects occur with the use of epidermal growth factor receptor inhibitors (EGFRI). In addition to the cutaneous inflammation induced by EGFRIs, these agents have been associated with the exacerbation of autoimmune skin disease and contact hypersensitivity, antiviral effects, and fatal alveolar damage in the setting of lung transplantation. Because EGFR ligands can modulate MHC class I (MHCI) and II (MHCII) molecule expression, we hypothesized that some of the immune-related effects of EGFRIs are due to direct effects on the expression of MHCI and/or MHCII molecules.
Experimental Design: Primary human keratinocytes and a malignant keratinocyte cell line (A431) were treated with EGFRIs alone or prior to IFN-γ, a potent inducer of MHCI and MHCII molecule expression. CIITA, MHCI, and MHCII RNA expression was measured using quantitative real-time reverse transcriptase PCR, and cell surface MHCI and MHCII protein expression was measured using flow cytometry. Skin biopsies from patients were analyzed for MHCI and MHCII protein expression before and during therapy with an EGFRI using immunohistochemistry.
Results: Both EGFR tyrosine kinase inhibitors and ligand-blocking antibodies (cetuximab) augmented the induction of MHCI and MHCII molecules by IFN-γ in primary and malignant human keratinocytes. Unexpectedly, the increase in MHCI protein expression did not require the presence of IFN-γ. Consistent with these in vitro findings, skin biopsies from cancer patients exhibited increased epidermal MHCI protein expression during therapy with an EGFRI as well as increases in MHCI and MHCII molecule RNA.
Conclusions: These studies suggest that EGFRIs may influence immune/inflammatory responses by directly modulating MHC expression. Clin Cancer Res; 17(13); 4400–13. ©2011 AACR.
Telomerase Peptide Vaccination Combined with Temozolomide: A Clinical Trial in Stage IV Melanoma Patients
Authors: Kyte Jon Amund , Gaudernack Gustav , Dueland Svein , Trachsel Sissel , Julsrud Lars , Aamdal Steinar 
Published: May 2011

AbstractPurpose: The study is a proof-of-principle trial evaluating toxicity, immune response, and clinical response in melanoma patients after combined therapy with temozolomide and the telomerase peptide vaccine GV1001. Our previous GV1001 trials showed immune responses in approximately 60% of lung or pancreatic cancer patients.Experimental Design: Twenty-five subjects with advanced stage IV melanoma (M1B or M1C) received concomitant temozolomide and GV1001. Temozolomide was administered 200 mg/m2 orally for 5 days every fourth week, and GV1001 as eight injections over 11 weeks. Immune response was evaluated by delayed type hypersensitivity, T-cell proliferation, and cytokine assays. The immunologic responders continued monthly vaccination.Results: The treatment was well tolerated. A GV1001-specific immune response was shown in 18 of 23 evaluated subjects (78%). Patients developing long-term T-cell memory survived more than those rapidly losing their responses. The immune response exhibited several characteristics of possible clinical significance including high IFNγ/IL-10 ratios, polyfunctional cytokine profiles, and recognition of naturally processed antigens. Survival compared favorably with matched controls from a benchmark meta-analysis (1 year: 44% vs. 24%, 2 years: 16% vs. 6.6%). The clinical responses developed gradually over years, contrary to what is expected from chemotherapy. Five patients developed partial tumor regression and six more recorded stable disease. One patient has no remaining disease on fluorodeoxyglucose positron emission tomography scans after 5 years.Conclusions: The immunologic response rate is considerable compared with previous GV1001 trials without concomitant chemotherapy, although low toxicity is retained. The results warrant further studies of GV1001/temozolomide treatment and support the general concept of combining cancer vaccination with chemotherapy. Clin Cancer Res; 17(13); 4568–80. ©2011 AACR.
Early G1 Cyclin-Dependent Kinases as Prognostic Markers and Potential Therapeutic Targets in Esophageal Adenocarcinoma
Authors: Ismail Amin , Bandla Santhoshi , Reveiller Marie , Toia Liana , Zhou Zhongren , Gooding William E. , Kalatskaya Irina , Stein Lincoln , D'Souza Mary , Litle Virginia R. , Peters Jeffrey H. , Pennathur Arjun , Luketich James D. , Godfrey Tony E. 
Published: May 2011

AbstractPurpose: Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this event has not been mapped with fine resolution in a large EAC cohort, and its association with clinical endpoints and functional relevance are unclear.Experimental Design: We used a cohort of 116 patients to fine map the 7q21 amplification using SNP microarrays. Prognostic significance and functional role of 7q21 amplification and its gene expression were explored.Results: Amplification of the 7q21 region was observed in 35% of tumors with a focal, minimal amplicon containing six genes. 7q21 amplification was associated with poor survival and analysis of gene expression identified cyclin-dependent kinase 6 (CDK6) as the only gene in the minimal amplicon whose expression was also associated with poor survival. A low-level amplification (10%) was observed at the 12q13 region containing the CDK6 homologue cyclin-dependent kinase 4 (CDK4). Both amplification and expression of CDK4 correlated with poor survival. A combined model of both CDK6 and CDK4 expressions is a superior predictor of survival than either alone. Specific knockdown of CDK4 and/or CDK6 by siRNAs shows that they are required for proliferation of EAC cells and that their function is additive. PD-0332991 targets the kinase activity of both molecules and suppresses proliferation and anchorage independence of EAC cells through activation of the pRB pathway.Conclusions: We suggest that CDK6 is the driver of 7q21 amplification and that both CDK4 and CDK6 are prognostic markers and bona fide oncogenes in EAC. Targeting these molecules may constitute a viable new therapy for this disease. Clin Cancer Res; 17(13); 4513–22. ©2011 AACR.
Time-Course Imaging of Therapeutic Functional Tumor Vascular Normalization by Antiangiogenic Agents
Authors: Zhang Qingbei , Bindokas Vytas , Shen Jikun , Fan Hanli , Hoffman Robert M. , Xing H. Rosie 
Published: May 2011

AbstractWe describe here new technology that enables noninvasive imaging of therapeutic functional normalization of tumor blood vessels by antiangiogenic agents. Noninvasive variable-magnification in vivo-fluorescence imaging as well as fluorescence tomography was used to visualize functional vessel normalization. Changes in the same vessel before and after drug treatment were imaged with high resolution in real time. Differences in vascular responses to the mTOR inhibitor rapamycin and to an anti-VEGF antibody were functionally imaged. Tumor vessel normalization was shown by significantly reduced leakiness and subsequent improved tumor delivery of Paclitaxel-BODPY as well as by normalized morphology. The tumor vascular pool agent, AngioSense750, was retained only in tumors after either anti-VEGF antibody or rapamycin treatment, as visualized by noninvasive fluorescence tomography. The antiangiogenic therapy normalized vessels, which significantly enhanced the antitumor efficacy of paclitaxel because of increased drug penetration throughout the tumor. The optical imaging technology described here is thus a powerful, noninvasive, time-course imaging tool of functional tumor vessel normalization and its therapeutic consequences. Mol Cancer Ther; 10(7); 1173–84. ©2011 AACR.