bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunization of High-Risk Breast Cancer Patients with Clustered sTn-KLH Conjugate plus the Immunologic Adjuvant QS-21
Authors: Gilewski Teresa A. , Ragupathi Govind , Dickler Maura , Powell Shemeeakah , Bhuta Sonal , Panageas Kathy , Koganty R. Rao , Chin-Eng Jeannette , Hudis Clifford , Norton Larry , Houghton Alan N. , Livingston Philip O. 
Published: May 2007

AbstractPurpose: To determine the clinical toxicities and antibody response against sTn and tumor cells expressing sTn following immunization of high-risk breast cancer patients with clustered sTn-KLH [sTn(c)-KLH] conjugate plus QS-21.Experimental Design: Twenty-seven patients with no evidence of disease and with a history of either stage IV no evidence of disease, rising tumor markers, stage II (≥4 positive axillary nodes), or stage III disease received a total of five injections each during weeks 1, 2, 3, 7, and 19. Immunizations consisted of sTn(c)-KLH conjugate containing 30, 10, 3, or 1 μg sTn(c) plus 100 μg QS-21. Induction of IgM and IgG antibodies against synthetic sTn(c) and natural sTn on ovine submaxillary mucin were measured before and after therapy. Fluorescence-activated cell sorting analyses assessed reactivity of antibodies to LSC and MCF-7 tumor cells.Results: The most common toxicities were transient local skin reactions at the injection site and mild flu-like symptoms. All patients developed significant IgM and IgG antibody titers against sTn(c). Antibody titers against ovine submaxillary mucin were usually of lower titers. IgM reactivity with LSC tumor cells was observed in 21 patients and with MCF-7 cells in 13 patients. There was minimal IgG reactivity with LSC cells.Conclusion: Immunization with sTn(c)-KLH conjugate plus QS-21 is well tolerated and immunogenic in high-risk breast cancer patients. Future trials will incorporate sTn(c) as a component of a multiple antigen vaccine.
Vascular Endothelial Growth Factor and Its Relationship to Inflammatory Mediators
Authors: Angelo Laura S. , Kurzrock Razelle 
Published: May 2007

Abstract
Inflammation occurs in response to host injury or infection, as the result of an autoimmune disease, or in response to the development of a tumor. Although the immune system may be helpful in fighting the tumor, it may also fuel the tumorigenic process. In fact, recent data suggest a strong link between chronic inflammation, angiogenesis, and the development of cancer. For example, inflammation and scarring caused by recurring infections with Mycobacterium tuberculosis may be a cause for cancers of the lung. Inflammatory breast cancer exhibits increased angiogenesis and lymphangiogenesis and has a higher metastatic potential than noninflammatory breast cancer. Nonsteroidal anti-inflammatory drugs have been proposed as preventives for the development of colon carcinoma and ovarian cancer. Inhibition of nuclear factor-κB contributes to the proposed mechanism of action. Inflammatory cytokines, including interleukin-6, serve as autocrine and paracrine growth factors for several cancers, and high levels of these cytokines may correlate with a poor prognosis and increased production of angiogenic factors. The state of the art of our understanding of this critical interaction is reviewed.
The Graft Content of Donor T Cells Expressing γδTCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors
Authors: Pabst Caroline , Schirutschke Holger , Ehninger Gerhard , Bornhäuser Martin , Platzbecker Uwe 
Published: May 2007

AbstractPurpose: Recently, high numbers of regulatory T cells within the stem cell graft were described to be associated with less graft-versus-host disease (GVHD) after related peripheral blood stem cell transplantation (PBSCT). Studies in mice also suggest a distinct role of γδTCR+ T cells in mediating GVHD. Therefore, the aim of this study was to define the yet-unknown role of regulatory and γδTCR+ T cells in human PBSCT from unrelated donors.Experimental Design: The frequency of both T-cell subsets within the graft was analyzed in 63 patients receiving unrelated allogeneic PBSCT. The respective amounts were quantified by flow cytometry and PCR and further correlated with clinical outcome.Results: The grafts contained a median of 11.2 × 106/kg CD4+foxp3+ and 9.8 × 106/kg γδTCR+ T cells, respectively. Patients receiving more CD4+foxp3+ cells had a lower cumulative incidence of acute GVHD II-IV (44% versus 65%, P = 0.03). Interestingly, in patients who received higher concentrations of donor γδTCR+ T cells, acute GVHD II-IV was more frequent (66% versus 40%, P = 0.02). In multivariate analysis, only the graft concentration of γδTCR+ T cells (P = 0.002) and a positive cytomegalovirus status of the recipient (P = 0.03) were significantly associated with the occurrence of acute GVHD II-IV.Conclusion: Graft composition of T-cell subsets seems to affect the outcome of patients receiving allogeneic PBSCT from unrelated donors. Therefore, selective manipulation or add-back of particular subsets might be a promising strategy to reduce the incidence of GVHD.
Microtubule-Associated Proteins as Targets in Cancer Chemotherapy
Authors: Bhat Kumar M.R. , Setaluri Vijayasaradhi 
Published: May 2007

Abstract
Natural and synthetic compounds that disrupt microtubule dynamics are among the most successful and widely used cancer chemotherapeutic agents. However, lack of reliable markers that predict sensitivity of cancers to these agents and development of resistance remain vexing issues. There is accumulating evidence that a family of cellular proteins that are associated with and alter the dynamics of microtubules can determine sensitivity of cancer cells to microtubule-targeting agents and play a role in tumor cell resistance to these agents. This growing family of microtubule-associated proteins (MAP) includes products of oncogenes, tumor suppressors, and apoptosis regulators, suggesting that alteration of microtubule dynamics may be one of the critical events in tumorigenesis and tumor progression. The objective of this review is to integrate the knowledge on these seemingly unrelated proteins that share a common function and examine their relevance to microtubule-targeting therapies and highlight MAPs-tubulin-drug interactions as a novel avenue for new drug discovery. Based on the available evidence, we propose that rational microtubule-targeting cancer therapeutic approaches should ideally include proteomic profiling of tumor MAPs before administration of microtubule-stabilizing/destabilizing agents preferentially in combination with agents that modulate the expression of relevant MAPs.
Magnetic Resonance Imaging Determination of Tumor Grade and Early Response to Temozolomide in a Genetically Engineered Mouse Model of Glioma
Authors: McConville Patrick , Hambardzumyan Dolores , Moody Jonathan B. , Leopold Wilbur R. , Kreger Alicia R. , Woolliscroft Michael J. , Rehemtulla Alnawaz , Ross Brian D. , Holland Eric C. 
Published: May 2007

Abstract
Purpose: The median survival for patients diagnosed with glioblastoma multiforme, the most common type of brain tumor, is less than 1 year. Animal glioma models that are more predictive of therapeutic response in human patients than traditional models and that are genetically and histologically accurate are an unmet need. The nestin tv-a (Ntv-a) genetically engineered mouse spontaneously develops glioma when infected with ALV-A expressing platelet-derived growth factor, resulting in autocrine platelet-derived growth factor signaling.
Experimental Design: In the Ntv-a genetically engineered mouse model, T2-weighted and T1-weighted, contrast-enhanced magnetic resonance images were correlated with histology, glioma grade (high or low), and survival. Magnetic resonance imaging (MRI) was therefore used to enroll mice with high-grade gliomas into a second study that tested efficacy of the current standard of care for glioma, temozolomide (100 mg/kg qdx5 i.p., n = 13).
Results: The Ntv-a model generated a heterogeneous group of gliomas, some with high-grade growth rate and histologic characteristics and others with characteristics of lower-grade gliomas. We showed that MRI could be used to predict tumor grade and survival. Temozolomide treatment of high-grade tv-a gliomas provided a 14-day growth delay compared with vehicle controls. Diffusion MRI measurement of the apparent diffusion coefficient showed an early decrease in cellularity with temozolomide, similar to that observed in humans.
Conclusions: The use of MRI in the Ntv-a model allows determination of glioma grade and survival prediction, distribution of mice with specific tumor types into preclinical trials, and efficacy determination both by tumor growth and early apparent diffusion coefficient response.
Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles
Authors: Hegde Priti S. , Rusnak David , Bertiaux Melissa , Alligood Krystal , Strum Jay , Gagnon Robert , Gilmer Tona M. 
Published: May 2007

AbstractLapatinib (GW572016) is a small-molecule dual inhibitor of epidermal growth factor receptor (ErbB1) and ErbB2 receptor kinase activities currently in phase III clinical trials. We used phosphoprotein and microarray analyses to carry out targeted pathway studies of phosphorylation and gene expression changes in human breast cancer cell lines in the presence or absence of lapatinib. Studies were done in four breast cancer cell lines, two of which were responsive and two of which were nonresponsive to lapatinib. Responsive cell lines, BT474 and SKBr3, constitutively overexpress ErbB2 and show an IC50 of 25 or 32 nmol/L for lapatinib, respectively. In contrast, nonresponsive MDA-MB-468 and T47D cells expressed a low basal level of ErbB2 and showed IC50 values in the micromolar range. Cells responsive to lapatinib exhibited strong differential effects on multiple genes in the AKT pathway. After 12 h of exposure to 1.0 μmol/L of lapatinib, AKT1, MAPK9, HSPCA, IRAK1, and CCND1 transcripts were down-regulated 7- to 25-fold in responsive BT474 and SKBr3 cells. In contrast, lapatinib weakly down-regulated the AKT pathway in nonresponsive breast cancer cell lines (&lt;5-fold down-regulation of most genes in the pathway). Furthermore, the proapoptotic gene FOXO3A, which is negatively regulated by AKT, was up-regulated 7- and 25-fold in lapatinib-responsive SKBr3 and BT474 cells, respectively. Phosphorylated Akt and Akt-mediated phosphorylation of FOXO3A also decreased in responsive breast cancer cell lines exposed to lapatinib. Gene expression profiling also revealed that lapatinib stimulated the expression of estrogen and progesterone receptors and modulated the expression of genes involved in cell cycle control, glycolysis, and fatty acid metabolism. In BT474 and T47D cells, which expressed moderate basal levels of the estrogen and progesterone receptors, 1.0 μmol/L of lapatinib induced expression by 7- to 11-fold. These data provide insight into the mechanism of action of lapatinib in breast cancer cells. [Mol Cancer Ther 2007;6(5):1629–40]
Classification of anti-estrogens according to intramolecular FRET effects on phospho-mutants of estrogen receptor α
Authors: Zwart Wilbert , Griekspoor Alexander , Rondaij Mariska , Verwoerd Desiree , Neefjes Jacques , Michalides Rob 
Published: May 2007

AbstractAnti-estrogen resistance is a major clinical problem in the treatment of breast cancer. In this study, fluorescence resonance energy transfer (FRET) analysis, a rapid and direct way to monitor conformational changes of estrogen receptor α (ERα) upon anti-estrogen binding, was used to characterize resistance to anti-estrogens. Nine different anti-estrogens all induced a rapid FRET response within minutes after the compounds have liganded to ERα in live cells, corresponding to an inactive conformation of the ERα. Phosphorylation of Ser305 and/or Ser236 of ERα by protein kinase A (PKA) and of Ser118 by mitogen-activated protein kinase (MAPK) influenced the FRET response differently for the various anti-estrogens. PKA and MAPK are both associated with resistance to anti-estrogens in breast cancer patients. Their respective actions can result in seven different combinations of phospho-modifications in ERα where the FRET effects of particular anti-estrogen(s) are nullified. The FRET response provided information on the activity of ERα under the various anti-estrogen conditions as measured in a traditional reporter assay. Tamoxifen and EM-652 were the most sensitive to kinase activities, whereas ICI-182,780 (Fulvestrant) and ICI-164,384 were the most stringent. The different responses of anti-estrogens to the various combinations of phospho-modifications in ERα elucidate why certain anti-estrogens are more prone than others to develop resistance. These data provide new insights into the mechanism of action of anti-hormones and are critical for selection of the correct individual patient-based endocrine therapy in breast cancer. [Mol Cancer Ther 2007;6(5):1526–33]
Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line
Authors: Herman-Antosiewicz Anna , Xiao Hui , Lew Karen L. , Singh Shivendra V. 
Published: May 2007

AbstractPrevious studies have indicated that d,l-sulforaphane (SFN), a synthetic cancer chemopreventive analogue of cruciferous vegetable-derived isomer (−)-1-isothiocyanato-(4R)-(methylsulfinyl)-butane, activates a checkpoint kinase 2 (Chk2)–dependent G2-M phase cell cycle arrest in p53-deficient human prostate cancer cells. Because p53 is a downstream target of Chk2 kinase and known to regulate G2-M transition by transcriptional regulation of cyclin-dependent kinase (Cdk) inhibitor p21Cip1/Waf1 (p21), the present study was undertaken to determine the role of p21 in SFN-induced cell cycle arrest using wild-type p53–expressing cell line LNCaP. The SFN treatment caused a modest increase in S phase fraction and a marked increase in G2-M fraction in LNCaP cells in a concentration- and time-dependent manner. The SFN-induced S phase arrest correlated with a reduction in protein levels of cyclin D1, cyclin E, Cdk4, and Cdk6, whereas activation of the G2-M checkpoint was accompanied by induction of cyclin B1 and down-regulation of Cdk1 and Cdc25C protein levels. The SFN-treated LNCaP cells were also arrested in mitosis as revealed by immunofluorescence microscopy and increased Ser10 phosphorylation of histone H3, a sensitive marker for mitotic cells. The SFN treatment increased activating phosphorylation of Chk2 (Thr68) that was accompanied by induction of p53 and p21. The SFN-induced mitotic arrest was statistically significantly increased by small interfering RNA–based knockdown of p21. However, p21 protein knockdown did not have any appreciable effect on SFN-induced cytoplasmic histone-associated DNA fragmentation (apoptosis). In conclusion, the present study indicates that induction of p21 protects against SFN-induced mitotic arrest in LNCaP cells. [Mol Cancer Ther 2007;6(5):1673–81]
RETRACTED: Modeling and Control of an Elastic Ship-mounted Crane Using Variable Gain Model-based Controller
Authors: Al-Sweiti Yousef , Söffker Dirk 
Published: May 2007

We, the editors and publishers of Mathematical and Computer Modelling of Dynamical Systems (Taylor & Francis) and Journal of Vibration & Control (SAGE) are retracting the following articles: A. Cargo pendulation suppression of ship cranes with elastic booms, Authors: D. Soeffker, Y.M Al- Sweiti*, Mathematical and Computer Modelling of Dynamical Systems, published by Taylor & Francis. Volume 13, Issue 6, 2007, pages 503–529 DOI: 10.1080/13873950701214424 B. Modelling and control of an elastic ship-mounted crane using variable-gain model-based controller, Yousef Al-Sweiti and Dirk Soeffker, Journal of Vibration & Control, published by SAGE. Volume 13, Issue 5, 2007, pages 657–685 DOI: 10.1177/1077546307074246 We are now aware that these articles contain sections that substantially overlap with each other and with the following published papers: 1. Yousef Al-Sweiti and Dirk Soeffker, "‘Modelling and control of an elastic ship-mounted crane using variable- gain model-based controller," Proceedings of the Institution of Mechanical Engineers, Part K: Journal of Multi-body Dynamics, December 1, 2006; vol. 220, 4: pp. 239–255. 2. Yousef Al-Sweiti and Dirk Soeffker, ‘"Planar cargo control of elastic ship cranes with the ‘‘Maryland Rigging’’ system,’’ Journal of Vibration and Control, March 2007, vol. 13, no. 3, pp. 241–267. It is noted that Article (1) has already been retracted by SAGE. We have conducted a detailed investigation with regards to the originality of Articles A and B, and have consulted with each other on the appropriate course of action. Taylor & Francis and SAGE are in agreement that Articles (A) and (B) bear substantial overlap to each other and Article (2), particularly in the Mathematical Modeling and Observer and Controller Design sections. The Publishers are thus retracting Articles A and B from publication in Mathematical and Computer Modelling of Dynamical Systems and Journal of Vibration and Control. The authors failed to cite, reference, or properly acknowledge their previous work nor properly identify or quote extracts from that work which subsequently appeared in, and appeared original to the articles (now retracted) in, Mathematical and Computer Modelling of Dynamical Systems and Journal of Vibration and Control. The authors were therefore in breach of the rules of submission for Mathematical and Computer Modelling of Dynamical Systems and Journal of Vibration and Control, and of the warranties made to both Taylor & Francis and SAGE regarding originality. We note that the Editors of Mathematical and Computer Modelling of Dynamical Systems and Journal of Vibration and Control published the now retracted articles in good faith. Taylor & Francis SAGE
HIV modulates the expression of ligands important in triggering natural killer cell cytotoxic responses on infected primary T-cell blasts
Authors: Ward Jeffrey , Bonaparte Matthew , Sacks Jennifer , Guterman Jacqueline , Fogli Manuela , Mavilio Domenico , Barker Edward 
Published: May 2007

AbstractThe ability of natural killer (NK) cells to kill virus-infected cells depends on the presence of ligands for activation receptors on the target cells. We found the presence of few, if any, NKp30 and NK46 ligands on T cell blasts infected with HIV, although NKp44 ligands were found on infected cells. HIV does induce the NKG2D ligands ULBP-1, -2, and -3. These ligands are involved in triggering NK cells to kill autologous HIV-infected cells, because interfering with the interaction between NKG2D, but not NKp46, on NK cells and its ligands on HIV-infected cells drastically reduced the lysis of infected cells. Interfering with the binding of the NK-cell coreceptors NTB-A and 2B4 to their ligands also decreased destruction by NK cells. The coreceptor ligands, NTB-A and CD48, were also found to be down-regulated during the course of HIV infection. Thus, ligands for NK-cell receptors are modulated during the course of HIV infection, which may greatly alter NK cells' ability to kill the infected cells.
Cell adhesion induces p27Kip1-associated cell-cycle arrest through down-regulation of the SCFSkp2 ubiquitin ligase pathway in mantle-cell and other non-Hodgkin B-cell lymphomas
Authors: Lwin Tint , Hazlehurst Lori A. , Dessureault Sophie , Lai Raymond , Bai Wenlong , Sotomayor Eduardo , Moscinski Lynn C. , Dalton William S. , Tao Jianguo 
Published: May 2007

Abstract
Mounting evidence suggests that dynamic interactions between a tumor and its microenvironment play a critical role in tumor development, cell-cycle progression, and response to therapy. In this study, we used mantle cell lymphoma (MCL) as a model to characterize the mechanisms by which stroma regulate cell-cycle progression. We demonstrated that adhesion of MCL and other non-Hodgkin lymphoma (NHL) cells to bone marrow stromal cells resulted in a reversible G1 arrest associated with elevated p27Kip1 and p21 (WAF1) proteins. The adhesion-mediated p27Kip1 and p21 increases were posttranslationally regulated via the down-regulation of Skp2, a subunit of SCFSkp2 ubiquitin ligase. Overexpression of Skp2 in MCL decreased p27Kip1, whereas inhibition of Skp2 by siRNA increased p27Kip1 and p21 levels. Furthermore, we found cell adhesion up-regulated Cdh1 (an activating subunit of anaphase-promoting complex [APC] ubiquitin ligase), and reduction of Cdh1 by siRNA induced Skp2 accumulation and hence p27Kip1 degradation, thus implicating Cdh1 as an upstream effector of the Skp2/p27Kip1 signaling pathway. Overall, this report, for the first time, demonstrates that cell-cell contact controls the tumor cell cycle via ubiquitin-proteasome proteolytic pathways in MCL and other NHLs. The understanding of this novel molecular pathway may prove valuable in designing new therapeutic approaches for modifying tumor cell growth and response to therapy.
Cardiac asthma in elderly patients: incidence, clinical presentation and outcome
Authors: Jorge Stéphane , Becquemin Marie-Hélène , Delerme Samuel , Bennaceur Mohamed , Isnard Richard , Achkar Rony , Riou Bruno , Boddaert Jacques , Ray Patrick 
Published: May 2007

AbstractBackgroundCardiac asthma is common, but has been poorly investigated. The objective was to compare the characteristics and outcome of cardiac asthma with that of classical congestive heart failure (CHF) in elderly patients.MethodsProspective study in an 1,800-bed teaching hospital.ResultsTwo hundred and twelve consecutive patients aged ≥ 65 years presenting with dyspnea due to CHF (mean age of 82 ± 8 years) were included. Findings of cardiac echocardiography and natriuretic peptides levels were used to confirm CHF. Cardiac asthma patients were defined as a patient with CHF and wheezing reported by attending physician upon admission to the emergency department. The CHF group (n = 137) and the cardiac asthma group (n = 75), differed for tobacco use (34% vs. 59%, p < 0.05), history of chronic obstructive pulmonary disease (16% vs. 47%, p < 0.05), peripheral arterial disease (10% vs. 24%, p < 0.05). Patients with cardiac asthma had a significantly lower pH (7.38 ± 0.08 vs. 7.43 ± 0.06, p < 0.05), and a higher PaCO2(47 ± 15 vs. 41 ± 11 mmHg, p < 0.05) at admission. In the cardiac asthma group, patients had greater distal airway obstruction: forced expiratory volume in 1 second of 1.09 vs. 1.33 Liter (p < 0.05), and a forced expiratory flow at 25% to 75% of vital capacity of 0.76 vs. 0.99 Liter (p < 0.05). The in-hospital (23% vs. 19%) and one year mortality (48% vs. 43%) rates were similar.ConclusionPatients with cardiac asthma represented one third of CHF in elderly patients. They were more hypercapnic and experienced more distal airway obstruction. However, outcomes were similar.