bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase II Study of Docetaxel and Epirubicin in Advanced Adult Soft Tissue Sarcomas (STS)
Authors: Kalofonos Haralabos P. , Kourousis Charalabos , Karamouzis Michalis V. , Iconomou Gregoris , Tsiata Ekaterini , Tzorzidis Fotis , Megas Panagiotis , Lambiris Elias , Georgoulias Vasilios 
Published: March 2011

Purpose: The aim of this study was to determine the efficacy and safety of docetaxel plus epirubicin combination as first‐line
chemotherapy in patients with locally advanced and/or metastatic adult STS.Patients and Methods: Eighteen patients were treated with epirubicin 30 mg/m2 on days 1 to 3 and docetaxel 100 mg/m2 on
day 1 every 3 weeks.Results: Fifteen out of 18 patients (83.4%) were assessable for response. No complete response was recorded. Three (20%)
patients achieved PR, 3 had SD and 9 PD. The overall median survival was 14 months (range, 3–48 months) and the median
time to disease progression was 4 months (range, 2–45 months). Grade ≥ 3 neutropenia occurred in 88% and neutropenic
fever in 27.8% of patients. Other toxicities were mild. No treatment related deaths occurred.Discussion: Docetaxel plus epirubicin combination achieved low response rate with severe myelotoxicity in patients with
advanced STS.
Immunohistochemical Loss of the DNA Mismatch Repair Proteins MSH2 and MSH6 in Malignant Fibrous Histiocytomas
Authors: Ericson Kajsa , Engellau Jacob , Persson Annette , Lindblom Annika , Domanski Henryk , Åkerman Måns , Nilbert Mef 
Published: March 2011

Purpose: Soft tissue sarcomas (STS) account for less than 1% of all malignancies and constitute a heterogeneous tumor entity in which malignant fibrous histiocytomas (MFH) represent one‐third and are characterized by a lack of type‐specific differentiation. A defective mismatch repair (MMR) system cause the familial cancer syndrome hereditary non‐polyposis colorectal cancer (HNPCC), and since occasional MFH have been described in HNPCC patients we assessed the contribution of defective MMR to the development of MFH.Methods: MMR status was characterized in a series of 209 histopathologically reviewed MFH. Tissue microarray sections from the tumors were immunohistochemically stained for the MMR proteins MLH1, MSH2 and MSH6, and cases with aberrant staining were further characterized for microsatellite instability.Results and Discussion: Two of the 209 STS–a storiform‐pleomorphic MFH and a myxofibrosarcoma–showed concomitant loss of MSH2 and MSH6, but retained staining for MLH1 on both cases. The myxoid tumor also had a microsatellite unstable phenotype. These findings, together with previous observations of defective MMR in pleomorphic STS, indicate that these tumors may be part of the HNPCC‐associated tumor spectrum and demonstrate that MMR defects occur in a small subset of STS.
A Phase II Study of Docetaxel for the Treatment of Recurrent Osteosarcoma
Authors: Mctiernan Anne , Whelan Jeremy S. 
Published: March 2011

Purpose: To determine the response and toxicity of docetaxel in recurrent osteosarcoma and related spindle cell tumours of bone.Patients and methods: Fourteen patients, 10 males and four females, were enrolled, median age 30.5 years (range, 17–46). Diagnosis was: conventional osteosarcoma, 12 patients; periosteal osteosarcoma, one patient; and malignant fibrous histiocytoma of bone, one patient. Initial chemotherapy had been with doxorubicin and cisplatin in 10 patients, and multiagent regimens in four. Nine had been treated with second line chemotherapy before receiving docetaxel. Thirteen patients had lung metastases and one intra‐abdominal disease. Docetaxel 100 mg/m2 was given as a 1‐h infusion every 3 weeks. Response was assessed every two cycles to a maximum of six.Results: A total of 43 cycles were given, median of two per patient (range 1–6). Thirteen patients were evaluable for response. A single partial remission was seen, for a response rate of 8%. Two patients had stable disease, and one patient a mixed response. Forty cycles were evaluable for toxicity. The principle toxicity was haematological, with a median neutrophil count of 0.9 (range 0–9.6). There were four episodes of neutropenic sepsis (10%). The only non‐haematological toxicity ≥grade 3 was stomatitis, occurring in just one patient. There were no toxic deaths.Conclusion: Docetaxel at this dose and schedule is well tolerated, but is not associated with significant activity in patients with relapsed osteosarcoma.
Phase II Trial of Dolastatin‐10, a Novel Anti‐Tubulin Agent, in Metastatic Soft Tissue Sarcomas
Authors: von Mehren M. , Balcerzak S. P. , Kraft A. S. , Edmonson J. H. , Okuno S. H. , Davey M. , Mclaughlin S. , Beard M. T. , Rogatko A. 
Published: March 2011

Patients:Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease.
Dolastatin‐10 (Dol‐10) is a pentapeptide anti‐microtubule agent that binds to tubulin sites distinct from vinca alkaloids.
Based on the novel mechanism of action, limited activity of other anti‐microtubular agents, and anti‐neoplastic activity in
pre‐clinical screening of Dol‐10, this multi‐institutional phase II study was conducted to determine the objective response
rate of Dol‐10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the
adjuvant setting.Methods: Dol‐10 was given intravenously at a dose of 400 μg/m2 and repeated every 21 days. Toxicities were assessed using
the Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cycles
to assess response [Miller AB, et al. Cancer 1981; 47(1): 207].Results: Dol‐10 was associated with hematological toxicity and with some vascular toxicities. There was no significant
gastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objective
responses in 12 patients treated with Dol‐10.Discussion: Based on this phase II trial, further study of Dol‐10 on this schedule is not recommended in advanced or
metastatic soft tissue sarcomas.
Liposarcoma of the Thyroid
Authors: Mitra A. , Fisher C. , Rhys-Evans P. , Harmer C. 
Published: March 2011

Liposarcoma of the thyroid gland is rare with only 3 cases reported in the English literature. We present a further two patients
whom we have recently treated: a 49 year old lady with a myxoid liposarcoma and a 71 year old man with a pleomorphic
liposarcoma. Both underwent macroscopic excision of tumour but had positive margins, so were then treated with external
beam radiotherapy. The former patient died from metastases 10 months after presentation, the latter remains alive but has
developed metastatic disease on follow up at 24 months.We recommend the use of high dose radiotherapy following radical surgery as margins of excision are usually narrow in
this most difficult region. The role of chemotherapy is yet to be established.
Novel Human Single Chain Antibody Fragments That Are Rapidly Internalizing Effectively Target Epithelioid and Sarcomatoid Mesotheliomas
Authors: Iyer Arun K. , Lan Xiaoli , Zhu Xiaodong , Su Yang , Feng Jinjin , Zhang Xiaoju , Gao Dongwei , Seo Youngho , VanBrocklin Henry F. , Broaddus V. Courtney , Liu Bin , He Jiang 
Published: March 2011

Abstract
Human antibodies targeting all subtypes of mesothelioma could be useful to image and treat this deadly disease. Here we report tumor targeting of a novel internalizing human single chain antibody fragment (scFv) labeled with 99mTc (99mTc-M40) in murine models of mesothelioma of both epithelioid (M28) and sarcomatoid (VAMT-1) origins. 99mTc-M40 was taken up rapidly and specifically by both subtype tumor cells in vitro, with 68% to 92% internalized within 1 hour. The specificity of binding was evidenced by blocking (up to 95%) with 10-fold excess of unlabeled M40. In animal studies, tumors of both subtypes were clearly visualized by SPECT/CT as early as 1 hour postinjection of 99mTc-M40. Tumor uptake measured as percent of injected dose per gram tissue (%ID/g) at 3 hours was 4.38 and 5.84 for M28 and VAMT-1 tumors, respectively, significantly greater than all organs or tissues studied (liver, 2.62%ID/g; other organs or tissues &lt;1.7%ID/g), except the kidneys (130.7%ID/g), giving tumor-to-blood ratios of 5:1 and 7:1 and tumor-to-muscle ratios of 45:1 and 60:1, for M28 and VAMT-1, respectively. The target-mediated uptake was confirmed by a nearly 70% reduction in tumor activity following administration of 10-fold excess of unlabeled scFv. Taken together, these results indicate that M40 can rapidly and specifically target epithelioid and sarcomatoid tumor cells, demonstrating the potential of this agent as a versatile targeting ligand for imaging and therapy of all subtypes of mesothelioma. Cancer Res; 71(7); 2428–32. ©2011 AACR.
Dynamic Changes of Edema and Late Gadolinium Enhancement After Acute Myocardial Infarction and Their Relationship to Functional Recovery and Salvage Index
Authors: Dall'Armellina Erica , Karia Nina , Lindsay Alistair C. , Karamitsos Theodoros D. , Ferreira Vanessa , Robson Matthew D. , Kellman Peter , Francis Jane M. , Forfar Colin , Prendergast Bernard D. , Banning Adrian P. , Channon Keith M. , Kharbanda Rajesh K. , Neubauer Stefan , Choudhury Robin P. 
Published: March 2011

Background—
Changes in the myocardium in acute ischemia are dynamic and complex, and the characteristics of myocardial tissue on cardiovascular magnetic resonance in the acute setting are not fully defined. We investigated changes in edema and late gadolinium enhancement (LGE) with serial imaging early after acute myocardial infarction, relating these to global and segmental myocardial function at 6 months.

Methods and Results—

Cardiovascular magnetic resonance scans were performed on 30 patients with ST-elevation–myocardial infarction treated by primary percutaneous coronary intervention at each of 4 time points: 12 to 48 hours; 5 to 7 days; 14 to 17 days; and 6 months. All patients showed edema at 24 hours. The mean volume of edema (% left ventricle) was 37±16 at 24 hours and 39±17 at 1 week, with a reduction to 24±13 (
P
<0.01) by 2 weeks. Myocardial segments with edema also had increased signal on LGE at 24 hours (κ=0.77;
P
<0.001). The volume of LGE decreased significantly between 24 hours and 6 months (27±15% versus 22±12%;
P
=0.002). Of segments showing LGE at 24 hours, 50% showed resolution by 6 months. In segments with such a reduction in LGE, 65% also showed improved wall motion (
P
<0.0001). The area of LGE measured at 6 months correlated more strongly with troponin at 48 hours (
r
=0.9;
P
<0.01) than LGE at 24 hours (
r
=0.7). The difference in LGE between 24 hours and 6 months had profound effects on the calculation of salvage index (26±21% at 24 hours versus 42±23% at 6 months;
P
=0.02).

Conclusions—
Myocardial edema is maximal and constant over the first week after myocardial infarction, providing a stable window for the retrospective evaluation of area at risk. By contrast, myocardial areas with high signal intensity in LGE images recede over time with corresponding recovery of function, indicating that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium.
Integrated regional water management: a study of collaboration or water politics-as-usual in California, USA
Authors: Lubell Mark , Lippert Lucas 
Published: March 2011

This article analyzes the effectiveness of Integrated Regional Water Management (IRWM) in the San Francisco Bay Area of California for decreasing fragmentation and increasing collaboration among water management stakeholders. The theory identifies the elements of traditional water management politics that lead to fragmentation and conflict. The water politics-as-usual model is then compared to the collaborative model of integrated water management. The evolution of IRWM in California is briefly described. A survey of Bay Area stakeholders is used to assess whether participation in the Bay Area IRWM achieves the goals of collaboration and integration. The basic results suggest that the Bay Area has made only incremental progress away from the fragmentation and conflict seen in the past. Points for practitioners Integrated Regional Water Management is not a panacea for policy fragmentation. Short-term increases in collaboration must be followed by consistent attention to on-the-ground implementation of integrative projects. IRWM is unlikely to cause immediate, drastic changes in policy implementation. Policy change will be incremental and decision-makers must assess whether stronger administrative measures are needed to continue the process of integration and collaboration. Traditionally powerful interests are likely to dominate IRWM decisions unless explicit steps are taken to empower previously excluded groups. The success of IRWM will vary across regions, and more research is needed to identify important contextual variables.
Symposium on water governance. Prologue: water governance as a government’s actions between the reality of fragmentation and the need for integration
Authors: Edelenbos Jurian , Teisman Geert R. 
Published: March 2011

This special issue on water governance pays attention to the aspect of fragmentation and integration from an international point of view. We want to give insights into how different countries — the USA, South America and Europe — are dealing with fragmentation in water issues. This first contribution was partly an introduction on the theme of water governance and the fragmentation—integration public administration discussion, and partly gave case illustrations from the Netherlands (two delta areas) in showing how fragmentation and attempts at integration took place. These two cases illustrated that fragmentation is manifest and attempts at integration are alive, but are often not effective. On the one hand (southwestern delta) integration is sought for through centralization (top-down coordination) and creating one overall formal structure (through legislation), on the other hand (IJsseldelta-South) we saw that integration is difficult to manage leading to crowding out and fading out effects (from central, regional integration efforts to local integration efforts). Points for practitioners Water resources, especially fresh water, will become one of the scarcest resources for humans, societies and ecosystems. In several areas of the world this is already quite evident. A third of the world’s population lives in water-stressed countries. Water governance is also crucial in terms of water surplus. Almost all the deltas in the world will face flooding problems, and three-quarters of the world’s population live in deltas. The joint starting point for this symposium on Water Governance is the existing fragmentation of responsibilities in this field. Achieving cooperation and integration in such fragmented systems is a core problem in governance.
Essential thrombocythemia versus early primary myelofibrosis: a multicenter study to validate the WHO classification
Authors: Thiele Jürgen , Kvasnicka Hans Michael , Müllauer Leonhard , Buxhofer-Ausch Veronika , Gisslinger Bettina , Gisslinger Heinz 
Published: March 2011

AbstractControversy persists regarding the role of histopathology in the distinction between essential thrombocythemia (ET) and early-prefibrotic primary myelofi-brosis (PMF) presenting with thrombocythemia. To investigate the impact and reproducibility of bone marrow (BM) morphology according to the World Health Organization classification, 295 patients with the presumptive clinical diagnosis of either ET or early PMF were studied. Data of this cohort (Vienna group) were compared with 732 corresponding patients (Cologne group). Evaluating blindly (only age and gender known) BM specimens, the 2 groups of pathologists achieved an overall consensus of 78% regarding the total series and 88% concerning the discrimination between ET versus PMF. In 126 ET and 81 early PMF patients without pretreatment and complete documentation, a 90% concordance with the independently established clinical diagnosis was found. In 12 patients, overlapping of histopathology and some clinical findings between ET and polycythemia vera occurred. Contrasting ET, early PMF showed significant differences of presenting hematologic data and an unfavorable prognosis (estimated mean survival, 14 vs 21 years). Comparison of clinical and survival data of the Vienna cohort with the historical Cologne series revealed an overall congruence. This study highlights the impact of BM morphology for the differentiation between true vs false ET.
Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNFα/NFκB pathway
Authors: Armanious Hanan , Gelebart Pascal , Anand Mona , Belch Andrew , Lai Raymond 
Published: March 2011

AbstractOne of the main functions of A Disintegrin and Metalloproteinase 10 (ADAM10) is to regulate the bioavailability of adhesion molecules and ligands to various cellular-signaling receptors. Constitutive activation of ADAM10 has been implicated in the pathogenesis of several types of solid tumors. In this study, we found that mantle cell lymphoma (MCL) cell lines and all 12 patient samples examined expressed the active/mature form of ADAM10. In contrast, PBMCs from healthy donors (n = 5) were negative. Using immunohistochemistry, ADAM10 was readily detectable in 20 of 23 (87%) MCL tumors, but absent in 5 reactive tonsils. Knockdown of ADAM10 using short interfering RNA (siRNA) in MCL cells significantly induced growth inhibition and cell-cycle arrest, and these changes were correlated with down-regulation of cyclin D1, up-regulation of p21waf1, and significant reductions in the TNFα production/transcriptional activity of NFκBp65. The addition of recombinant ADAM10 to MCL cells led to the opposite biologic effects. Lastly, down-regulation of ADAM10 using siRNA enhanced the growth-suppressing effects mediated by the proteasome inhibitors MG132 and bortezomib. We conclude that constitutive activation of ADAM10 contributes to the growth of MCL and therefore inhibition of ADAM10 may be a useful strategy to enhance the response of MCL to other therapeutic agents.
Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy
Authors: Gutiérrez-García Gonzalo , Cardesa-Salzmann Teresa , Climent Fina , González-Barca Eva , Mercadal Santiago , Mate José L. , Sancho Juan M. , Arenillas Leonor , Serrano Sergi , Escoda Lourdes , Martínez Salomé , Valera Alexandra , Martínez Antonio , Jares Pedro , Pinyol Magdalena , García-Herrera Adriana , Martínez-Trillos Alejandra , Giné Eva , Villamor Neus , Campo Elías , Colomo Luis , López-Guillermo Armando ,   for the Grup per l'Estudi dels Limfomes de Catalunya I Balears (GELCAB)
Published: March 2011

Abstract
Diffuse large B-cell lymphomas (DLBCLs) can be divided into germinal-center B cell–like (GCB) and activated-B cell–like (ABC) subtypes by gene-expression profiling (GEP), with the latter showing a poorer outcome. Although this classification can be mimicked by different immunostaining algorithms, their reliability is the object of controversy. We constructed tissue microarrays with samples of 157 DLBCL patients homogeneously treated with immunochemotherapy to apply the following algorithms: Colomo (MUM1/IRF4, CD10, and BCL6 antigens), Hans (CD10, BCL6, and MUM1/IRF4), Muris (CD10 and MUM1/IRF4 plus BCL2), Choi (GCET1, MUM1/IRF4, CD10, FOXP1, and BCL6), and Tally (CD10, GCET1, MUM1/IRF4, FOXP1, and LMO2). GEP information was available in 62 cases. The proportion of misclassified cases by immunohistochemistry compared with GEP was higher when defining the GCB subset: 41%, 48%, 30%, 60%, and 40% for Colomo, Hans, Muris, Choi, and Tally, respectively. Whereas the GEP groups showed significantly different 5-year progression-free survival (76% vs 31% for GCB and activated DLBCL) and overall survival (80% vs 45%), none of the immunostaining algorithms was able to retain the prognostic impact of the groups (GCB vs non-GCB). In conclusion, stratification based on immunostaining algorithms should be used with caution in guiding therapy, even in clinical trials.
Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans
Authors: Stuehler Claudia , Khanna Nina , Bozza Silvia , Zelante Teresa , Moretti Silvia , Kruhm Michaela , Lurati Sarah , Conrad Barbara , Worschech Eike , Stevanović Stefan , Krappmann Sven , Einsele Hermann , Latgé Jean-Paul , Loeffler Juergen , Romani Luigina , Topp Max S. 
Published: March 2011

AbstractT cell–mediated heterologous immunity to different pathogens is promising for the development of immunotherapeutic strategies. Aspergillus fumigatus and Candida albicans, the 2 most common fungal pathogens causing severe infections in immunocompromised patients, are controlled by CD4+ type 1 helper T (TH1) cells in humans and mice, making induction of fungus-specific CD4+ TH1 immunity an appealing strategy for antifungal therapy. We identified an immunogenic epitope of the A fumigatus cell wall glucanase Crf1 that can be presented by 3 common major histocompatibility complex class II alleles and that induces memory CD4+ TH1 cells with a diverse T-cell receptor repertoire that is cross-reactive to C albicans. In BALB/c mice, the Crf1 protein also elicits cross-protection against lethal infection with C albicans that is mediated by the same epitope as in humans. These data illustrate the existence of T cell–based cross-protection for the 2 distantly related clinically relevant fungal pathogens that may foster the development of immunotherapeutic strategies.
Lysophosphatidic acid suppresses endothelial cell CD36 expression and promotes angiogenesis via a PKD-1–dependent signaling pathway
Authors: Ren Bin , Hale James , Srikanthan Sowmya , Silverstein Roy L. 
Published: March 2011

AbstractIn pathologic settings including retinal ischemia and malignant tumors, robust angiogenesis occurs despite the presence in the microenvironment of antiangiogenic proteins containing thrombospondin structural homology (TSR) domains. We hypothesized that antiangiogenesis mediated by TSR-containing proteins could be blunted by localized down-regulation of their cognate receptor on microvascular endothelial cells (MVECs), CD36. Through screening a panel of endothelial cell agonists, we found that lysophosphatidic acid (LPA) dramatically down-regulated CD36 surface expression on primary MVECs. LPA is a lipid-signaling mediator known to have proangiogenic activity, but the mechanisms are largely unknown. We observed that LPA caused CD36 down-regulation in a dose- and time-dependent manner and was long lasting. Down-regulation occurred at the transcriptional level via a signaling pathway involving specific LPA receptors and protein kinase D. LPA-induced MVEC CD36 repression significantly attenuated in vitro antiangiogenic responses to thrombospondin-1, including blockade of migration, tube formation, and VEGFR-2 signaling in response to fibroblast growth factor-2. In vivo relevance was demonstrated by showing that LPA abrogated thrombospondin-1–mediated inhibition of neovascularization of Matrigel plugs implanted in mice. Our data thus indicate that the proangiogenic mechanism of LPA may in part be via switching off the antiangiogenic switch mediated by TSR proteins and CD36.