bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the Little Fire Ant, Wasmannia auropunctata, on Native Forest Ants in Gabon1
Authors: Walker Kendra L. 
Published: July 2006

ABSTRACTThe Neotropical little fire ant, Wasmannia auropunctata, is notorious for its negative impacts on the native biota of tropical islands, such as the Galapagos and New Caledonia, where it has been introduced. Here, I evaluate the impact of exotic W. auropunctata populations on continental Africa. I surveyed ants at nine sites in Lopé National Park in Gabon, Central Africa, and found a highly significant correlation between ant diversity and length of infestation by W. auropunctata. I found many more native ant species present in areas not infested with W. auropunctata (39.0 ± 4.6) compared with areas infested by W. auropunctata for approximately 5–10 yr (7.0 ± 6.2 and 1.7 ± 1.2, respectively). In infested areas, W. auropunctata made up the bulk of specimens collected in every plot. This study demonstrates that the threat posed by W. auropunctata to biodiversity is as serious in continental ecosystems as it is in the more fragile island ecosystems of previous studies. Introductions near waterways are particularly devastating: in Lopé, the infested territory is most extensive along waterways and occurs in a pattern that strongly suggests moving water facilitates colonization.
Electron Paramagnetic Resonance Oxygen Images Correlate Spatially and Quantitatively with Oxylite Oxygen Measurements
Authors: Elas Martyna , Ahn Kang-Hyun , Parasca Adrian , Barth Eugene D. , Lee David , Haney Chad , Halpern Howard J. 
Published: July 2006

Abstract
Tumor oxygenation predicts cancer therapy response and malignant phenotype. This has spawned a number of oxymetries. Comparison of different oxymetries is crucial for the validation and understanding of these techniques. Electron paramagnetic resonance (EPR) imaging is a novel technique for providing quantitative high-resolution images of tumor and tissue oxygenation. This work compares sequences of tumor pO2 values from EPR oxygen images with sequences of oxygen measurements made along a track with an Oxylite oxygen probe. Four-dimensional (three spatial and one spectral) EPR oxygen images used spectroscopic imaging techniques to measure the width of a spectral line in each image voxel from a trityl spin probe (OX063, Amersham Health R&D) in the tissues and tumor of mice after spin probe injection. A simple calibration allows direct, quantitative translation of each line width to an oxygen concentration. These four-dimensional EPR images, obtained in 45 minutes from FSa fibrosarcomas grown in the legs of C3H mice, have a spatial resolution of ∼1 mm and oxygen resolution of ∼3 Torr. The position of the Oxylite track was measured within a 2-mm accuracy using a custom stereotactic positioning device. A total of nine images that involve 17 tracks were obtained. Of these, most showed good correlation between the Oxylite measured pO2 and a track located in the tumor within the uncertainties of the Oxylite localizability. The correlation was good both in terms of spatial distribution pattern and pO2 magnitude. The strong correlation of the two modalities corroborates EPR imaging as a useful tool for the study of tumor oxygenation.
High WT1 Expression Is Associated with Very Poor Survival of Patients with Osteogenic Sarcoma Metastasis
Authors: Srivastava Alok , Fuchs Bruno , Zhang Kunbo , Ruan Ming , Halder Chandralekha , Mahlum Eric , Weber Kristin , Bolander Mark E. , Sarkar Gobinda 
Published: July 2006

Abstract
Purpose: Although metastasis is the primary determinant of poor survival of patients with osteogenic sarcoma, some patients live much longer than others, indicating metastatic heterogeneity underlying survival outcome. The purpose of the investigation was to identify genes underlying survival outcome of patients with osteogenic sarcoma metastasis.
Experimental Design: We have used microarray to first compare mRNA expression between normal bone and osteogenic sarcoma specimens, identified genes overexpressed in osteogenic sarcoma, and compared expression of the selected gene between a poorly metastatic (SAOS) and two highly metastatic cell lines (LM8 and 143B). Finally, expression of the selected gene was assessed by immunostaining of osteogenic sarcoma samples with known survival outcome.
Results: Microarray analysis revealed 5.3-fold more expression of WT1 mRNA in osteogenic sarcoma compared with normal bone and &gt;2-fold overexpression in 143B and LM8 cells compared with SAOS. Furthermore, WT1 mRNA was absent in normal bone (10 of 10) by reverse transcription-PCR but present in osteogenic sarcoma–derived cell lines (5 of 8). One hundred percent (42 of 42) of low-grade osteogenic sarcoma specimens expressed no WT1 as determined by immunostaining; however, 24% (12 of 49) of the high-grade specimens showed intense staining. Mean survival of patients with high-grade metastatic osteogenic sarcoma but low WT1 staining (27 of 37) was 96.5 ± 129.3 months, whereas mean survival of patients with high-grade metastatic osteogenic sarcoma having intense staining (10 of 37) was 18.3 ± 12.3 months (P &gt; 0.0143). All splice variants of WT1 mRNA, including a hitherto unknown variant (lacking exons 4 and 5), were found to be expressed in osteogenic sarcoma.
Conclusion: WT1 seems to be associated with very poor survival of patients with osteogenic sarcoma metastasis.
Influence of Formulation Vehicle on Metronomic Taxane Chemotherapy: Albumin-Bound versus Cremophor EL–Based Paclitaxel
Authors: Ng Sylvia S.W. , Sparreboom Alex , Shaked Yuval , Lee Christina , Man Shan , Desai Neil , Soon-Shiong Patrick , Figg William D. , Kerbel Robert S. 
Published: July 2006

AbstractPurpose: Low-dose metronomic chemotherapy treatments, especially when combined with ‘dedicated’ antiangiogenic agents, can induce significant antitumor activity without serious toxicity in various preclinical models. It remains unclear, however, whether some cytotoxic drugs are better suited for metronomic regimens than others. Paclitaxel appears to be a strong candidate for metronomic chemotherapy given its ability to inhibit endothelial cell functions relevant to angiogenesis in vitro at extraordinarily low concentrations and broad-spectrum antitumor activity. Clinically relevant concentrations of the formulation vehicle cremophor EL in Taxol, however, were previously reported to nullify the antiangiogenic effect of paclitaxel, the result of which would hamper its usefulness in metronomic regimens. We hypothesized that ABI-007, a cremophor EL–free, albumin-bound, 130-nm form of paclitaxel, could potentially alleviate this problem.Experimental Design: The antiangiogenic activity of ABI-007 was assessed by multiple in vitro assays. The in vivo optimal dose of ABI-007 for metronomic chemotherapy was determined by measuring circulating endothelial progenitors in peripheral blood. The antitumor effects of metronomic and maximum tolerated dose ABI-007 and Taxol were then evaluated and compared in severe combined immunodeficient mice bearing human MDA-MD-231 breast cancer and PC3 prostate cancer xenografts.Results: ABI-007 significantly inhibited rat aortic microvessel outgrowth, human endothelial cell proliferation, and tube formation. The optimal metronomic dose of ABI-007 was determined to be between 3 and 10 mg/kg. Metronomic ABI-007 but not Taxol, significantly suppressed tumor growth in both xenograft models. Furthermore, the antitumor effect of minimally toxic metronomic ABI-007 approximated that of the maximum tolerated dose of Taxol.Conclusions: Our results underscore the influence of formulation vehicles on the selection of cytotoxic drugs for metronomic chemotherapy.
Chronic Oxaliplatin Resistance Induces Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cell Lines
Authors: Yang Anthony D. , Fan Fan , Camp E. Ramsay , van Buren George , Liu Wenbiao , Somcio Ray , Gray Michael J. , Cheng Haiyun , Hoff Paulo M. , Ellis Lee M. 
Published: July 2006

Abstract
Purpose: Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire molecular alterations that facilitate cell motility and invasion. In preliminary studies, we observed that oxaliplatin-resistant (OxR) colorectal cancer (CRC) cells underwent morphologic changes suggestive of a migratory phenotype, leading us to hypothesize that OxR CRC cells undergo EMT.
Experimental Design: The human CRC cell lines KM12L4 and HT29 were exposed to increasing doses of oxaliplatin to establish stable cell lines resistant to oxaliplatin. Migration and invasion were assessed by modified Boyden chamber assays. Morphologic and molecular changes characteristic of EMT were determined by immunofluorescence staining and Western blot analyses.
Results: The OxR cells showed phenotypic changes consistent with EMT: spindle-cell shape, loss of polarity, intercellular separation, and pseudopodia formation. KM12L4 and HT29 OxR cells exhibited an ∼8- to 15-fold increase in migrating and invading cells, respectively (P &lt; 0.005 for both). Immunofluorescence staining of OxR cells revealed translocation of E-cadherin and β-catenin from their usual membrane-bound complex to the cytoplasm and nucleus, respectively. The OxR cells also had decreased expression of the epithelial adhesion molecules E-cadherin and plakoglobin and an increase in the mesenchymal marker vimentin. The KM12L4 OxR cells exhibited increased nuclear expression of Snail, an EMT-regulatory transcription factor, whereas the HT29 OxR cells exhibited an increase in nuclear expression of the EMT-associated transcription factor nuclear factor κB.
Conclusion: We hypothesize that induction of EMT may contribute to the decreased efficacy of therapy in chemoresistant CRC, as the tumor cells switch from a proliferative to invasive phenotype. Further understanding of the mechanisms of chemoresistance in CRC will enable improvements in chemotherapy for metastatic disease.
Systemic Anti-CD25 Monoclonal Antibody Administration Safely Enhances Immunity in Murine Glioma without Eliminating Regulatory T Cells
Authors: Fecci Peter E. , Sweeney Alison E. , Grossi Peter M. , Nair Smita K. , Learn Christopher A. , Mitchell Duane A. , Cui Xiuyu , Cummings Thomas J. , Bigner Darell D. , Gilboa Eli , Sampson John H. 
Published: July 2006

AbstractPurpose: Elevated proportions of regulatory T cells (Treg) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined Tregs in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct.Experimental Design: CD4+CD25+Foxp3+GITR+ Tregs were quantified in the peripheral blood, spleens, cervical lymph nodes, and bone marrow of mice bearing malignant glioma. The capacities for systemic anti-CD25 therapy to deplete Tregs, enhance lymphocyte function, and generate antiglioma CTL responses were assessed. Lastly, survival and experimental allergic encephalitis risks were evaluated when anti-CD25 was combined with a dendritic cell–based immunization targeting shared tumor and central nervous system antigens.Results: Similar to patients with malignant glioma, glioma-bearing mice show a CD4 lymphopenia. Additionally, CD4+CD25+Foxp3+GITR+ Tregs represent an increased fraction of the remaining peripheral blood CD4+ T cells, despite themselves being reduced in number. Similar trends are observed in cervical lymph node and spleen, but not in bone marrow. Systemic anti-CD25 administration hinders detection of CD25+ cells but fails to completely eliminate Tregs, reducing their number only moderately, yet eliminating their suppressive function. This elimination of Treg function permits enhanced lymphocyte proliferative and IFN-γ responses and up to 80% specific lysis of glioma cell targets in vitro. When combined with dendritic cell immunization, anti-CD25 elicits tumor rejection in 100% of challenged mice without precipitating experimental allergic encephalitis.Conclusions: Systemic anti-CD25 administration does not entirely eliminate Tregs but does prevent Treg function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and Treg compartments seen in patients with malignant glioma.
Selecting Lung Cancer Patients for Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors by Immunohistochemistry and FluorescenceIn situHybridization—Why, When, and How?
Authors: Dziadziuszko Rafal , Hirsch Fred R. , Varella-Garcia Marileila , Bunn Paul A. 
Published: July 2006

AbstractRecent evidence indicates that high epidermal growth factor receptor (EGFR) gene copy number evaluated by fluorescence in situ hybridization is an excellent predictive biomarker for response and survival benefit in patients with non–small cell lung cancer who receive epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Data on EGFR protein expression by immunohistochemistry as a selection marker are conflicting, although several studies showed that the treatment benefit was confined to EGFR-positive patients. Our studies and others showed that fluorescence in situ hybridization and immunohistochemistry were associated with the best predictive value. Expeditious validation of this information in prospective clinical trials with patient selection to first-line treatment is currently being done or planned by several cancer research groups worldwide.
Genomic Approaches to Lung Cancer
Authors: Thomas Roman K. , Weir Barbara , Meyerson Matthew 
Published: July 2006

AbstractThe last decade has seen remarkable success in clinical targeting of activated oncogenes in cancer. We have applied gene expression profiling, high-density single-nucleotide polymorphism arrays, and systematic resequencing of genes to identify novel oncogenes and signaling pathways in lung cancer that might represent therapeutic targets. Systematic resequencing of tyrosine kinase genes has led to the discovery of somatic mutations in the epidermal growth factor receptor (EGFR) gene in lung adenocarcinomas. These mutations range in frequency from 10% in Caucasian to 40% in East Asian patients. Lung cancer–derived EGFR mutations are oncogenic and are tightly associated with clinical response to the EGFR kinase inhibitors erlotinib and gefitinib. Furthermore, gene expression profiling has been shown to classify patients according to their clinical outcome, indicating that the application of this technique may help in guiding patient selection for therapy in the future. Finally, genome-wide analyses of copy number gains and losses were successfully applied to detect gene amplifications and deletions. Taken together, the application of genomics technologies has led to important discoveries with clinical implications in lung cancer that might help to improve clinical care for patients suffering from this highly fatal tumor.
The Synthetic Triterpenoid CDDO-Imidazolide Suppresses STAT Phosphorylation and Induces Apoptosis in Myeloma and Lung Cancer Cells
Authors: Liby Karen , Voong Nga , Williams Charlotte R. , Risingsong Renee , Royce Darlene B. , Honda Tadashi , Gribble Gordon W. , Sporn Michael B. , Letterio John J. 
Published: July 2006

Abstract
Purpose: Excessive activity of the transcription factors known as signal transducers and activators of transcription (STAT) contributes to the development and progression of malignancy in many organs. It is, therefore, important to develop new drugs to control the STATs, particularly their phosphorylation state, which is required for their transcriptional activity.
Experimental Design: Myeloma and lung cancer cells were treated with the new synthetic triterpenoid CDDO-Imidazolide, and STAT phosphorylation and apoptosis were evaluated by immunoblotting and fluorescence-activated cell sorting analysis.
Results: We now report that CDDO-Imidazolide, previously shown to be a potent agent for control of inflammation, cell proliferation, and apoptosis, rapidly (within 30-60 minutes) and potently (at nanomolar levels) suppresses either constitutive or interleukin-6-induced STAT3 and STAT5 phosphorylation in human myeloma and lung cancer cells. Furthermore, in these cells, CDDO-Imidazolide also up-regulates critical inhibitors of STATs, such as suppressor of cytokine signaling-1 and SH2-containing phosphatase-1 (a tyrosine phosphatase). Moreover, gene array studies reported here show that CDDO-Imidazolide potently regulates the transcription of important genes that are targets of the STATs.
Conclusions: Our new data thus show that CDDO-Imidazolide is a potent suppressor of STAT signaling and provide a further mechanistic basis for future clinical use of this agent to control inflammation or cell proliferation.
Epidermal Growth Factor Receptor Inhibitors in Development for the Treatment of Non–Small Cell Lung Cancer
Authors: Heymach John V. , Nilsson Monique , Blumenschein George , Papadimitrakopoulou Vassiliki , Herbst Roy 
Published: July 2006

Abstract
The epidermal growth factor receptor (EGFR) inhibitors erlotinib, gefitinib, and cetuximab have undergone extensive clinical testing and have established clinical activity in non–small cell lung cancer and other types of solid tumors. A number of newer inhibitors are currently in clinical development with different spectra of activity or mechanisms of receptor inhibition. These include monoclonal antibodies, such as panitumumab and matuzumab; dual inhibitors of EGFR and vascular endothelial growth factor receptor, such as ZD6474 and AEE788; inhibitors of multiple EGFR family members, such as lapatinib; and irreversible inhibitors, such as canertinib and HKI272. Preclinical studies suggest that several of these agents may have activity in tumors refractory to erlotinib or gefitinib. Among these agents, ZD6474 has undergone the most extensive clinical testing. The antitumor activity of ZD6474 in these two randomized phase II clinical trials in patients with non–small cell lung cancer was felt to be sufficiently promising to warrant phase III clinical testing. Several of the other EGFR inhibitors are also undergoing advanced clinical testing, either alone or in combination with other agents. EGFR has now been validated as a clinically relevant target, and several different types of agents inhibiting this receptor are currently in development. Future research will be needed to elucidate the role of these agents in patients with EGFR inhibitor–naive and EGFR inhibitor–refractory disease, to define the molecular characteristics that predict response, and to determine whether these drugs should be used in combination with other targeted agents or chemotherapy.
Isolation of Human Prostatic Epithelial Plasma Membranes for Proteomics Using Mirror Image Tissue Banking of Radical Prostatectomy Specimens
Authors: Sircar Kanishka , Gaboury Louis , Ouadi Lydia , Mecteau Melanie , Scarlata Eleonora , Saad Fred , Aprikian Armen , Tanguay Simon , Lapointe Steven , Lussier Christian , Miletti Tina , Lanoix Joel 
Published: July 2006

Abstract
Purpose: To isolate human prostatic epithelial plasma membranes for the identification of cell surface proteins in the therapeutic targeting of cancer cells while permitting the retrieval of banked samples for clinical purposes.
Experimental Design: Radical prostatectomies from 84 patients (median, 61 years; prostate-specific antigen, 5.9; 66% nonpalpable) were processed with alternate, mirror image slices submitted for histology and tissue banking. Benign and malignant foci were macrodissected from the banked sections using the pathologically mapped, mirror image histology sections as a guide. Epithelial plasma membranes were isolated using novel immunomagnetic purification and their purity was assessed. Tissue homogenates were probed by Western blot for malignant (AMACR) and benign (p63) markers to test the accuracy of this protocol. Selected banked tissue slices were retrieved, thawed, and compared pathologically to their corresponding routinely processed alternate slices.
Results: Plasma membrane preparations showed the enrichment of epithelial plasma membrane markers (prostate-specific membrane antigen and epithelial-specific antigen) with minimal marker expression from nonepithelial cells or intracellular organelles. Cancer homogenates showed up-regulated AMACR and down-regulated p63, whereas benign homogenates showed up-regulated p63 and down-regulated AMACR. There was 30% benign (p63+) contamination in cancer slices and &lt;6% cancer (AMACR+) contamination in benign slices. Retrieved tissues showed the retention of immunoreactivity while their histology was always adequate for diagnosis.
Conclusions: We have successfully isolated purified epithelial plasma membranes from benign and malignant human prostates and provided validation data for the accuracy of our protocol in a prostate-specific antigen–screened cohort. Our method also enabled the retrieval of banked tissues for clinical purposes with the retention of good histologic and immunohistochemical quality.
Basoluminal Carcinoma: A New Biologically and Prognostically Distinct Entity Between Basal and Luminal Breast Cancer
Authors: Laakso Mervi , Tanner Minna , Nilsson Jonas , Wiklund Tom , Erikstein Björn , Kellokumpu-Lehtinen Pirkko , Malmström Per , Wilking Nils , Bergh Jonas , Isola Jorma 
Published: July 2006

Abstract
Purpose: Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that is typically hormone receptor negative and shows a distinct gene expression profile. Based on variable basal cytokeratin immunostaining patterns, we hypothesized that the “basal phenotype” tumor group may comprise more than one biological entity.
Experimental Design: Basal cytokeratins 5 and 14 (CK5/14) were stained by immunohistochemistry and the percentage of positive cells was defined by image analysis. The results thus obtained were compared with clinicopathologic characteristics and relapse-free survival.
Results: Of the 506 breast tumors, 53 (10.5%) showed immunoreactivity for CK5/14. Basal cytokeratin expression showed up as two microscopically distinguishable subtypes, i.e., a uniformly positive type (“basal”) and a partially positive type (“basoluminal”) often displaying a checkerboard-type intratumoral heterogeneity. These subgroups could also be separated with a third basal cytokeratin (CK17, P &lt; 0.0001). Both basal and basoluminal subtypes were hormone receptor negative and of high grade, but differed with respect to the Ki-67 labeling index (P = 0.0014), vimentin (P = 0.005), and c-kit (P = 0.02), which were more frequently expressed in basal than in basoluminal tumors. In contrast, the amplification of HER-2 was found almost exclusively in the basoluminal subgroup (P = 0.009). Compared with the basal tumors, basoluminal tumors associated with significantly shorter relapse-free survival (P = 0.01), which was not explained by their more frequent HER-2 amplification.
Conclusions: We conclude that the intratumoral heterogeneity in basal cytokeratin expression can be used to define two distinct breast cancer subtypes, basal and basoluminal, with distinctive features related to proliferation activity, oncogene and biomarker status, and patient survival.