bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoledronic Acid as a New Adjuvant Therapeutic Strategy for Ewing's Sarcoma Patients
Authors: Odri Guillaume A. , Dumoucel Sophie , Picarda Gaëlle , Battaglia Séverine , Lamoureux François , Corradini Nadège , Rousseau Julie , Tirode Franck , Laud Karine , Delattre Olivier , Gouin François , Heymann Dominique , Redini Françoise 
Published: September 2010

Abstract
Ewing's sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 μg/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G2M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy. Cancer Res; 70(19); 7610–9. ©2010 AACR.
Functional MicroRNA Is Transferred between Glioma Cells
Authors: Katakowski Mark , Buller Benjamin , Wang Xinli , Rogers Thomas , Chopp Michael 
Published: September 2010

Abstract
MicroRNAs (miRNA) are single-stranded 17- to 27-nucleotide RNA molecules that regulate gene expression by posttranscriptional silencing of target mRNAs. Here, we transformed rat 9L gliosarcoma cells to express cel-miR-67, a miRNA that lacks homology in rat. Coculture of these cells with cells that expressed a luciferase reporter that contained a complementary sequence to cel-miR-67 resulted in significant suppression of luciferase expression. This effect was also observed in the U87-MG human glioma cell line. Moreover, luciferase suppression was inhibited by the addition of carbenoxolone to cocultures, suggesting that gap junction communication regulates intercellular transfer of miRNA. Finally, in situ hybridization revealed the presence of cel-miR-67 in cel-miR-67–null 9L cells after coculture with cel-miR-67–expressing cells. Our data show that miRNA transcribed in glioma cells can be transferred to adjacent cells and induces targeted inhibition of protein expression in the acceptor cells. These findings reveal a novel mechanism of targeted intercellular protein regulation between brain tumor cells. Cancer Res; 70(21); 8259–63. ©2010 AACR.
Macrophage Expression of Hypoxia-Inducible Factor-1α Suppresses T-Cell Function and Promotes Tumor Progression
Authors: Doedens Andrew L. , Stockmann Christian , Rubinstein Mark P. , Liao Debbie , Zhang Na , DeNardo David G. , Coussens Lisa M. , Karin Michael , Goldrath Ananda W. , Johnson Randall S. 
Published: September 2010

AbstractT cells can inhibit tumor growth, but their function in the tumor microenvironment is often suppressed. Many solid tumors exhibit abundant macrophage infiltration and low oxygen tension, yet how hypoxic conditions may affect innate immune cells and their role in tumor progression is poorly understood. Targeted deletion of the hypoxia-responsive transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages in a progressive murine model of breast cancer resulted in reduced tumor growth, although vascular endothelial growth factor-A levels and vascularization were unchanged. Tumor-associated macrophages can suppress tumor-infiltrating T cells by several mechanisms, and we found that hypoxia powerfully augmented macrophage-mediated T-cell suppression in vitro in a manner dependent on macrophage expression of HIF-1α. Our findings link the innate immune hypoxic response to tumor progression through induction of T-cell suppression in the tumor microenvironment. Cancer Res; 70(19); 7465–75. ©2010 AACR.
Aggressive Fibromatosis (Desmoid Tumor) Is Derived from Mesenchymal Progenitor Cells
Authors: Wu Colleen , Nik-Amini Saied , Nadesan Puviindran , Stanford William L. , Alman Benjamin A. 
Published: September 2010

Abstract
The cellular origins from which most tumors arise are poorly defined, especially in mesenchymal neoplasms. Aggressive fibromatosis, also known as desmoid tumor, is a locally invasive soft tissue tumor that has mesenchymal characteristics. We found that aggressive fibromatosis tumors express genes and cell surface markers characteristic of mesenchymal stem cells (MSC). In mice that are genetically predisposed to develop aggressive fibromatosis tumors (Apcwt/1638N), we found that the number of tumors formed was proportional to the number of MSCs present. Sca-1−/− mice, which develop fewer MSCs, were crossed with Apcwt/1638N mice. Doubly mutant mice deficient in Sca-1 developed substantially fewer aggressive fibromatosis tumors than wild-type (WT) littermates, but Sca-1 deficiency had no effect on the formation of epithelial-derived intestinal polyps. MSCs isolated from Apcwt/1638N mice (or mice expressing a stabilized form of β-catenin) induced aberrant cellular growth reminiscent of aggressive fibromatosis tumors after engraftment to immunocompromised mice, but WT cells and mature fibroblasts from the same animals did not. Taken together, our findings indicate that aggressive fibromatosis is derived from MSCs, and that β-catenin supports tumorigenesis by maintaining mesenchymal progenitor cells in a less differentiated state. Protecting this progenitor cell population might prevent tumor formation in patients harboring a germline APC mutation, where fibromatosis is currently the leading cause of mortality. Cancer Res; 70(19); 7690–8. ©2010 AACR.
Clinical Pharmacology of Resveratrol and Its Metabolites in Colorectal Cancer Patients
Authors: Patel Ketan R. , Brown Victoria A. , Jones Donald J.L. , Britton Robert G. , Hemingway David , Miller Andrew S. , West Kevin P. , Booth Tristan D. , Perloff Marjorie , Crowell James A. , Brenner Dean E. , Steward William P. , Gescher Andreas J. , Brown Karen 
Published: September 2010

Abstract
Resveratrol is a phytochemical with chemopreventive activity in preclinical rodent models of colorectal carcinogenesis. Antiproliferation is one of the many chemopreventive modes of action it has been shown to engage in. Concentrations of resveratrol, which can be achieved in human tissues after p.o. administration, have not yet been defined. The purpose of this study was to measure concentrations of resveratrol and its metabolites in the colorectal tissue of humans who ingested resveratrol. Twenty patients with histologically confirmed colorectal cancer consumed eight daily doses of resveratrol at 0.5 or 1.0 g before surgical resection. Resveratrol was found to be well tolerated. Normal and malignant biopsy tissue samples were obtained before dosing. Parent compound plus its metabolites resveratrol-3-O-glucuronide, resveratrol-4′-O-glucuronide, resveratrol-3-O-sulfate, resveratrol-4′-O-sulfate, resveratrol sulfate glucuronide, and resveratrol disulfate were identified by high-performance liquid chromatography (HPLC) with UV or mass spectrometric detection in colorectal resection tissue. Quantitation was achieved by HPLC/UV. Cell proliferation, as reflected by Ki-67 staining, was compared in preintervention and postintervention tissue samples. Resveratrol and resveratrol-3-O-glucuronide were recovered from tissues at maximal mean concentrations of 674 and 86.0 nmol/g, respectively. Levels of resveratrol and its metabolites were consistently higher in tissues originating in the right side of the colon compared with the left. Consumption of resveratrol reduced tumor cell proliferation by 5% (P = 0.05). The results suggest that daily p.o. doses of resveratrol at 0.5 or 1.0 g produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anticarcinogenic effects. Resveratrol merits further clinical evaluation as a potential colorectal cancer chemopreventive agent. Cancer Res; 70(19); 7392–9. ©2010 AACR.
Overexpression of the Protein Tyrosine Phosphatase PRL-2 Correlates with Breast Tumor Formation and Progression
Authors: Hardy Serge , Wong Nau Nau , Muller William J. , Park Morag , Tremblay Michel L. 
Published: September 2010

Abstract
The PRL-1, PRL-2, and PRL-3 phosphatases are prenylated protein tyrosine phosphatases with oncogenic activity that are proposed to drive tumor metastasis. We found that PRL-2 mRNA is elevated in primary breast tumors relative to matched normal tissue, and also dramatically elevated in metastatic lymph nodes compared with primary tumors. PRL-2 knockdown in metastatic MDA-MB-231 breast cancer cells decreased anchorage-independent growth and cell migration, suggesting that the malignant phenotype of these cells is mediated at least in part through PRL-2 signaling. In different mouse mammary tumor–derived cell lines overexpressing PRL-2, we confirmed its role in anchorage-independent growth and cell migration. Furthermore, injection of PRL-2–overexpressing cells into the mouse mammary fat pad promoted extracellular signal-regulated kinase 1/2 activation and tumor formation. MMTV–PRL-2 transgenic mice engineered to overexpress the enzyme in mammary tissue did not exhibit spontaneous tumorigenesis, but they exhibited an accelerated development of mammary tumors initiated by introduction of an MMTV-ErbB2 transgene. Together, our results argue that PRL-2 plays a role in breast cancer progression. Cancer Res; 70(21); 8959–67. ©2010 AACR.
Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species–Mediated Cellular Senescence
Authors: Lee Inkyoung , Park Chaehwa , Kang Won Ki 
Published: September 2010

Abstract
Senescence is an important determinant of treatment outcome in cancer therapy. In the present study, we show that knockdown of the inwardly rectifying K+ channel Kir2.2 induced growth arrest without additional cellular stress in cancer cells lacking functional p53, p16, and/or Rb. Kir2.2 knockdown also induced senescence-associated β-galactosidase activity and upregulated senescence marker proteins in multiple cancer cell lines derived from different tissues, including prostate, stomach, and breast. Interestingly, knockdown of Kir2.2 induced a significant increase in reactive oxygen species (ROS) that was accompanied by cell cycle arrest, characterized by significant upregulation of p27, with concomitant downregulation of cyclinA, cdc2, and E2F1. Kir2.2 knockdown cells displayed increased levels of PML bodies, DNA damage (γH2AX) foci, senescence-associated heterochromatin foci, mitochondrial dysfunction, secretory phenotype, and phosphatase inactivation. Conversely, overexpression of Kir2.2 decreased doxorubicin-induced ROS accumulation and cell growth inhibition. Kir2.2 knockdown-induced cellular senescence was blocked by N-acetylcysteine, indicating that ROS is a critical mediator of this pathway. In vivo tumorigenesis analyses revealed that tumors derived from Kir2.2 knockdown cells were significantly smaller than those derived from control cells (P &lt; 0.0001) and showed a remarkable increase in senescence-associated proteins, including senescence-associated β-galactosidase, p27, and plasminogen activator inhibitor-1. Moreover, the preestablished tumors are reduced in size after the injection of siKir2.2 (P = 0.0095). Therefore, we propose for the first time that Kir2.2 knockdown induces senescence of cancer cells by a mechanism involving ROS accumulation that requires p27, but not Rb, p53, or p16. Mol Cancer Ther; 9(11); 2951–9. ©2010 AACR.
Transcriptional Attenuation in Colon Carcinoma Cells in Response to Butyrate
Authors: Daroqui Maria C. , Augenlicht Leonard H. 
Published: September 2010

AbstractThe short-chain fatty acid sodium butyrate (NaB), produced in the colonic lumen, induces cell cycle arrest, differentiation, and/or apoptosis in colorectal carcinoma cells in vitro, establishing a potential role for NaB in colon cancer prevention. We have previously shown that butyrate decreases cyclin D1 and c-myc expression, each essential for intestinal tumor development, by transcriptional attenuation. Here, we determined that butyrate-induced transcriptional attenuation of the cyclin D1 and c-myc genes in SW837 human colorectal adenocarcinoma cells occurs at ∼100 nucleotides downstream of the transcription start site, with a similar positioning in Caco-2 cells. A concomitant decrease in RNA polymerase II occupancy at the 5′ end of each gene was observed. Because transcriptional regulation is associated with chromatin remodeling, we investigated by chromatin immunoprecipitation whether the histone deacetylase inhibitory activity of butyrate altered chromatin structure at the attenuated loci. Although the distributions of histone H3 trimethylated on K4 and K36 along the cyclin D1 and c-myc genes were consistent with current models, butyrate induced only modest decreases in these modifications, with a similar effect on acetylated H3 and a modest increase in histone H3 trimethylated on K27. Finally, transcriptome analysis using novel microarrays showed that butyrate-induced attenuation is widespread throughout the genome, likely independent of transcriptional initiation. We identified 42 loci potentially paused by butyrate and showed that the transcription patterns are gene specific. The biological functions of these loci encompass a number of effects of butyrate on the physiology of intestinal epithelial cells. Cancer Prev Res; 3(10); 1292–302. ©2010 AACR.
Effects of benzyl isothiocyanate on the reproduction of Meloidogyne incognita on Glycine max and Capsicum annuum
Authors: Masler Edward P. , Zasada Inga A. , Sardanelli Sandra , Rogers Stephen T. , Halbrendt John M. 
Published: September 2010

Abstract
Reproduction of Meloidogyne incognita on either Capsicum annuum or Glycine max was suppressed when infective second-stage juveniles (J2) were exposed to 0.03 mM benzyl isothiocyanate (BITC) for 2 h prior to inoculation of the host. Infectivity as rated by a gall index was significantly reduced on both G. max and C. annuum. In C. annuum, nematode egg masses were recovered from 48% of the plants inoculated with BITC-treated J2 compared with 98% for the controls, and egg mass scores were reduced. Egg mass production was reduced in C. annuum by 69% and mean total eggs/plant was reduced by 97% in G. max. When plants were inoculated with treated J2, two measures of plant health, root weight and shoot weight, were reduced in C. annuum but not in G. max. However, root and shoot weights were not correlated with egg production for either host plant, irrespective of treatment. There were strong interactions between egg production, as measured by mean total eggs/plant (G. max) or mean total eggs/egg mass (C. annuum), and hatching of J2 from eggs obtained from all combinations of plant host and J2 treatment. Hatch of J2 from eggs obtained from G. max was significantly lower when plants had been inoculated with BITC-treated J2 than when plants had been inoculated with control J2. Such effects were not observed with C. annuum. BITC may have important residual consequences on the progeny of M. incognita not directly exposed to the chemical.
Concentration of β-ecydisone (20E) in susceptible and resistant accessions of Pfaffia glomerata infected with Meloidogyne incognita and histological characterisation of resistance
Authors: Gomes Ana Cristina M.M. , Nicole Michel , Mattos Jean Kleber , Pereira Sarazete Izidia Vaz , Pereira Paulo , Silva Dijalma B. , Vieira Roberto , De Capdeville Guy , Moita Antônio W. , Carneiro Regina M.D.G. 
Published: September 2010

Abstract
Pfaffia glomerata is a medicinal plant widely distributed in Brazil, which is considered the world's greatest supplier of P. glomerata roots. Among active ingredients contained in this plant, the steroid β-ecydisone (20E) is the most important compound extracted from roots. This steroid presents therapeutic properties for the treatment of diabetes and haemorrhoids, besides having bioenergy, tonic and aphrodisiac effects. The root-knot nematode Meloidogyne spp. is a major limiting factor in root production. Recent studies showed resistance of accessions of P. glomerata to Meloidogyne incognita. The aims of this work were: i) to correlate the concentration of 20E with resistance and susceptibility of P. glomerata accessions to M. incognita in inoculated and non-inoculated plants; ii) to study the effect of the parasitism of M. incognita on the concentration of the steroid 20E in the roots; and iii) to clarify resistance mechanisms by comparing the response of a highly resistant UFV with a highly susceptible accession (Farm) to nematode infection. The concentration of 20E in the healthy susceptible Farm accession was significantly higher than in the healthy resistant UFV accession, showing that the resistance mechanism was not related to 20E concentrations. Plants of the Farm accession infected with M. incognita showed higher levels of 20E than the non-infected control. A positive and significant Pearson correlation coefficient was observed between 20E concentrations and gall indexes. Resistance of UFV to the root-knot nematode M. incognita was associated with unidentified factors that limited nematode penetration or emigration of second-stage juveniles and with post-penetration responses, including the hypersensitive response. Giant cells were sometimes found in the resistant cultivar, but displayed a highly vacuolated and degraded cytoplasm with thinner cell walls than those induced in the susceptible accession. Microscope observations under UV light showed a strong autofluorescence, suggesting that phenolic compounds may be involved in ginseng UFV resistance.
New and known species of Enoplolaimus (Enoplida: Thoracostomopsidae) from the Sea of Japan
Authors: Fadeeva Natalia P. , Zograf Julia K. 
Published: September 2010

Abstract
Two new thoracostomopsid species, Enoplolaimus pectinatus sp. n., E. patrokli sp. n., and one known species, E. medius, from the Sea of Japan, are described and illustrated with the aid of LM and LSM pictures. Enoplolaimus pectinatus sp. n. belongs to a group of species lacking a preanal supplementary organ and differs from the other species in this group by the shape of the spicules and the gubernaculum, which has a plate-like triangular crura provided with a comb of 14 denticles. Enoplolaimus patrokli sp. n. is characterised by the straight spicules and also differs from other species by the shape of the gubernaculum which has a plate-like cuneus with a dorsal, V-like, thickening and a small proximal dorsal process. Additional information is provided for E. medius on the basis of confocal microscopy. The structure of the head and spicules of E. medius is described. A pictorial key for the genus Enoplolaimus is proposed.
Superoxide dismutase isoelectric focusing patterns as a tool to differentiate pathotypes of Globodera spp.
Authors: Molinari Sergio , Greco Nicola , Zouhar Miloslav 
Published: September 2010

Abstract
Isoelectric focusing was used to separate proteins from cyst extracts of potato cyst nematode (PCN) populations. In a first set of assays, cyst extracts from standard populations of Globodera rostochiensis pathotypes Ro1, Ro2, Ro3, Ro2/3, Ro4, and Ro5, and G. pallida pathotypes Pa2 and Pa3, were loaded on isoelectric focusing gels. Gels were stained for superoxide dismutase (SOD), esterase, and glucose-6-phosphate isomerase (GPI). Twelve bands of SOD activity were detected, six (B1-B6) migrating towards the basic zone and the other six (A1-A6) migrating towards the acidic zone, starting from the loading point. A cluster analysis was carried out based on a data matrix that reported the presence or absence of SOD bands on the isozyme electrophoresis patterns (IEPs). Globodera spp. were clearly distinguished and, within G. rostochiensis, Ro2 and Ro4 shared a high level of similarity, respectively, with Ro3 and Ro5; moreover, Ro1 could be clearly distinguished from Ro2/3 and Ro4/5. Globodera pallida Pa2 and Pa3 also shared a high level of similarity. In contrast, esterase and GPI IEPs did not discriminate among G. rostochiensis standard pathotypes. Subsequently, 14 field populations of G. rostochiensis, five from Italy and nine from Venezuela, and three field populations of G. pallida, two from Italy and one from Chile, were assayed to obtain SOD IEPs. Italian populations had previously been identified at pathotype level by bioassays according to the generally accepted international test using different resistant potato cultivars and clones. The cluster analysis carried out on the SOD IEPs of all the populations tested formed four distinct groups within G. rostochiensis and only one within G. pallida. Pathotype identification of Globodera populations by SOD IEPs was not able to discriminate between bioassay standard couples Ro2/Ro3, Ro4/Ro5 and Pa2/Pa3. Therefore, three groups were assigned to Ro1, Ro2/3 and Ro4/5, and a fourth group to Pa2/Pa3. Four Venezuelan populations, not identified at pathotype level by bioassays, formed a distinct fifth group. By means of the method described herein, four additional unknown Venezuelan populations could be assigned to Ro1 group and one to Ro2/Ro3 group; one G. pallida population from Chile was assigned to Pa2/Pa3 group.
Marine nematode taxonomy in the age of DNA: the present and future of molecular tools to assess their biodiversity
Authors: da Silva Neyvan Renato Rodrigues , da Silva Maria Cristina , Fonseca Genevois Verônica , Esteves André Morgado , Ley Paul De , Decraemer Wilfrida , Rieger Tania Tassinari , dos Santos Correia Maria Tereza 
Published: September 2010

Abstract
Molecular taxonomy is one of the most promising yet challenging fields of biology. Molecular markers such as nuclear and mitochondrial genes are being used in a variety of studies surveying marine nematode taxa. Sequences from more than 600 species have been deposited to date in online databases. These barcode sequences are assigned to 150 nominal species from 104 genera. There are 41 species assigned to Enoplea and 109 species to Chromadorea. Morphology-based surveys are greatly limited by processing speed, while barcoding approaches for nematodes are hampered by difficulties in matching sequence data with morphology-based taxonomy. DNA barcoding is a promising approach because some genes contain variable regions that are useful to discriminate species boundaries, discover cryptic species, quantify biodiversity and analyse phylogeny. We advocate a combination of several approaches in studies of molecular taxonomy, DNA barcoding and conventional taxonomy as a necessary step to enhance the knowledge of biodiversity of marine nematodes.