bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bryostatin 1 modulates β-catenin subcellular localization and transcription activity through protein kinase D1 activation
Authors: Jaggi Meena , Chauhan Subhash C. , Du Cheng , Balaji K.C. 
Published: September 2008

AbstractIn recent years, the use of natural products for cancer prevention and treatment has received considerable attention. Bryostatin 1 is a natural macrocyclic lactone and a protein kinase D (PKD) modulator with potent antineoplastic properties that has been used to treat human cancers in clinical trials with limited success. Further understanding the mechanistic basis of Bryostatin 1 action may provide opportunities to improve clinical results of treatment with Bryostatin 1. We identified that PKD1, founding member of PKD family of serine/threonine kinases, modulates E-cadherin/β-catenin activity, which plays an important role in cell integrity, polarity, growth, and morphogenesis. An aberrant expression and localization of E-cadherin/β-catenin has been strongly associated with cancer progression and metastasis. In this study, we examined the effect of Bryostatin 1 treatment on PKD1 activation, β-catenin translocation and transcription activity, and malignant phenotype of prostate cancer cells. Initial activation of PKD1 with Bryostatin 1 leads to colocalization of the cytoplasmic pool of β-catenin with PKD1, trans-Golgi network markers, and proteins involved in vesicular trafficking. Activation of PKD1 by Bryostatin 1 decreases nuclear β-catenin expression and β-catenin/TCF transcription activity. Activation of PKD1 alters cellular aggregation and proliferation in prostate cancer cells associated with subcellular redistribution of E-cadherin and β-catenin. For the first time, we have identified that Bryostatin 1 modulates β-catenin signaling through PKD1, which identifies a novel mechanism to improve efficacy of Bryostatin 1 in clinical settings. [Mol Cancer Ther 2008;7(9):2703–12]
Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides
Authors: de Wolf Cornelia , Jansen Robert , Yamaguchi Hiroaki , de Haas Marcel , van de Wetering Koen , Wijnholds Jan , Beijnen Jos , Borst Piet 
Published: September 2008

Abstract
We have studied the potential contribution of ABCG2 (breast cancer resistance protein) to resistance to nucleoside analogues. In cells transfected with DNA constructs resulting in overexpression of human or mouse ABCG2, we found resistance against cladribine, clofarabine, fludarabine, 6-mercaptopurine, and 6-mercaptopurine riboside in both MDCKII and HEK293 cells and against gemcitabine only in HEK293 cells. With Transwell studies in MDCK cells and transport experiments with vesicles from Sf9 and HEK293 cells, we show that ABCG2 is able to transport not only the nucleotide CdAMP, like several other ATP-binding cassette transporters of the ABCC (multidrug resistance protein) family, but also the nucleoside cladribine itself. Expression of ABCG2 in cells results in a substantial decrease of intracellular CdATP, explaining the resistance against cladribine. The high transport rate of cladribine and clofarabine by ABCG2 deduced from Transwell experiments raises the possibility that this transporter could affect the disposition of nucleoside analogues in patients or cause resistance in tumors. [Mol Cancer Ther 2008;7(9):3092–102]
The Anterior N1 Component as an Index of Modality Shifting
Authors: Töllner Thomas , Gramann Klaus , Müller Hermann J. , Eimer Martin 
Published: September 2008

Abstract
Processing of a given target is facilitated when it is defined within the same (e.g., visual–visual), compared to a different (e.g., tactile–visual), perceptual modality as on the previous trial [Spence, C., Nicholls, M., & Driver, J. The cost of expecting events in the wrong sensory modality. Perception & Psychophysics, 63, 330–336, 2001]. The present study was designed to identify electrocortical (EEG) correlates underlying this “modality shift effect.” Participants had to discriminate (via foot pedal responses) the modality of the target stimulus, visual versus tactile (Experiment 1), or respond based on the target-defining features (Experiment 2). Thus, modality changes were associated with response changes in Experiment 1, but dissociated in Experiment 2. Both experiments confirmed previous behavioral findings with slower discrimination times for modality change, relative to repetition, trials. Independently of the target-defining modality, spatial stimulus characteristics, and the motor response, this effect was mirrored by enhanced amplitudes of the anterior N1 component. These findings are explained in terms of a generalized “modality-weighting” account, which extends the “dimension-weighting” account proposed by Found and Müller [Searching for unknown feature targets on more than one dimension: Investigating a “dimension-weighting” account. Perception & Psychophysics, 58, 88–101, 1996] for the visual modality. On this account, the anterior N1 enhancement is assumed to reflect the detection of a modality change and initiation of the readjustment of attentional weight-setting from the old to the new target-defining modality in order to optimize target detection.
Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation
Authors: Granell Miquel , Urbano-Ispizua Álvaro , Pons Aina , Aróstegui Juan Ignacio , Gel Bernat , Navarro Alfons , Jansa Sonia , Artells Rosa , Gaya Anna , Talarn Carme , Fernández-Avilés Francesc , Martínez Carmen , Rovira Montserrat , Carreras Enric , Rozman Ciril , Juan Manel , Yagüe Jordi , Montserrat Emili , Monzó Mariano 
Published: September 2008

Abstract
The inflammasomes are macromolecular cytosolic complexes involved in the production of interleukin-1β (IL-1β) and IL-18 in response to several pathogen-derived stimuli. Such interleukins have been implicated in the origin of severe allogeneic stem cell transplant (allo-SCT) complications. We analyzed the relationship between the interindividual variability in inflammasome protein-encoding genes in donors and patients and clinical outcome after allo-SCT. Fourteen common genetic variants in 5 genes of the inflammasome, namely, NLRP1, NLRP2, NLRP3, CARD8, and CASP5, were genotyped in 133 human leukocyte antigen-identical sibling pairs undergoing allo-SCT. In the multivariate analysis, donor variants in NLRP2 and NLRP3 were the most important prognostic factors for the clinical outcome after allo-SCT. Thus, donor TT genotype at rs10925027 in NLRP3 was associated with disease relapse (odds ratio (OR) = 6.3, P = 1 × 10−7), and donor GG genotype at rs1043684 in NLRP2 was associated with nonrelapse mortality (OR = 4.4, P = 6 × 10−4) and overall survival (OR = 3.1, P = .001). In addition, patient AA genotype at rs5862 in NLRP1 was associated with nonrelapse mortality (OR = 2.8, P = .005) and overall survival (OR = 2.0, P = .009). These results suggest that inflammasome genetic variants are important prognostic factors for the outcome of allo-SCT. If validated in larger studies, including unrelated allo-SCT, NLRPs genotype would become an important factor in donor selection.
Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts
Authors: Wakkach Abdelilah , Mansour Anna , Dacquin Romain , Coste Emmanuel , Jurdic Pierre , Carle Georges F. , Blin-Wakkach Claudine 
Published: September 2008

AbstractFinding that activated T cells control osteoclast (OCL) differentiation has revealed the importance of the interactions between immune and bone cells. Dendritic cells (DCs) are responsible for T-cell activation and share common precursors with OCLs. Here we show that DCs participate in bone resorption more directly than simply through T-cell activation. We show that, among the splenic DC subsets, the conventional DCs have the higher osteoclastogenic potential in vitro. We demonstrate that conventional DCs differentiate into functional OCLs in vivo when injected into osteopetrotic oc/oc mice defective in OCL resorptive function. Moreover, this differentiation involves the presence of activated CD4+ T cells controlling a high RANK-L expression by bone marrow stromal cells. Our results open new insights in the differentiation of OCLs and DCs and offer new basis for analyzing the relations between bone and immune systems.
Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera
Authors: Marchetti Marina , Castoldi Elisabetta , Spronk Henri M. H. , van Oerle René , Balducci Donatella , Barbui Tiziano , Rosing Jan , ten Cate Hugo , Falanga Anna 
Published: September 2008

Abstract
We used the thrombin generation assay to evaluate the hypercoagulable state according to JAK2V617F mutational status in essential thrombocythemia (ET) and polycythemia vera (PV) patients. Thrombin generation was determined in the presence and absence of activated protein C (APC), and APC resistance was expressed as normalized APC sensitivity ratio (nAPCsr). Tissue factor pathway inhibitor (TFPI), total and free protein S (PS), prothrombin (FII), factor V (FV), and neutrophil elastase were measured in plasma; CD11b was measured on neutrophils. Compared with normal controls, patients had a lower endogenous thrombin potential in the absence of APC but had a higher endogenous thrombin potential in the presence of APC, showing the occurrence of APC resistance. The nAPCsr increased in JAK2V617F carriers compared with noncarriers and was highest in JAK2V617F homozygous patients. FII, FV, free PS, and TFPI levels were reduced in patients, mainly in JAK2V617F carriers. Multiple regression analysis indicated the low free PS level as major determinant of the increased nAPCsr. Elastase was increased in patients and inversely correlated with free PS. In conclusion, these data indicate the occurrence of acquired APC resistance in ET and PV patients, probably because of a reduction in free PS levels. The APC-resistant phenotype is influenced by the JAK2V617F mutational load.
Docking of molecules identified in bioactive medicinal plants extracts into the p50 NF-kappaB transcription factor: correlation with inhibition of NF-kappaB/DNA interactions and inhibitory effects on IL-8 gene expression
Authors: Piccagli Laura , Fabbri Enrica , Borgatti Monica , Bezzerri Valentino , Mancini Irene , Nicolis Elena , Dechecchi Maria C , Lampronti Ilaria , Cabrini Giulio , Gambari Roberto 
Published: September 2008

Abstract

Background
The transcription factor NF-kappaB is a very interesting target molecule for the design on anti-tumor, anti-inflammatory and pro-apoptotic drugs. However, the application of the widely-used molecular docking computational method for the virtual screening of chemical libraries on NF-kappaB is not yet reported in literature. Docking studies on a dataset of 27 molecules from extracts of two different medicinal plants to NF-kappaB-p50 were performed with the purpose of developing a docking protocol fit for the target under study.

Results
We enhanced the simple docking procedure by means of a sort of combined target- and ligand-based drug design approach. Advantages of this combination strategy, based on a similarity parameter for the identification of weak binding chemical entities, are illustrated in this work with the discovery of a new lead compound for NF-kappaB. Further biochemical analyses based on EMSA were performed and biological effects were tested on the compound exhibiting the best docking score. All experimental analysis were in fairly good agreement with molecular modeling findings.

Conclusion
The results obtained sustain the concept that the docking performance is predictive of a biochemical activity. In this respect, this paper represents the first example of successfully individuation through molecular docking simulations of a promising lead compound for the inhibition of NF-kappaB-p50 biological activity and modulation of the expression of the NF-kB regulated IL8 gene.
Clinicopathologic features and outcomes following surgery for pancreatic adenosquamous carcinoma
Authors: Hsu Jun-Te , Chen Han-Ming , Wu Ren-Chin , Yeh Chun-Nan , Yeh Ta-Sen , Hwang Tsann-Long , Jan Yi-Yin , Chen Miin-Fu 
Published: September 2008

Abstract

Background
Pancreatic adenosquamous carcinoma (ASC) is a rare pancreatic malignancy subtype. We investigated the clinicopathological features and outcome of pancreatic ASC patients after surgery.

Methods
The medical records of 12 patients with pancreatic ASC undergoing surgical treatment (1993 to 2006) were retrospectively reviewed. Survival data of patients with stage IIB pancreatic adenocarcinoma and ASC undergoing surgical resection were compared.

Results
Symptoms included abdominal pain (91.7%), body weight loss (83.3%), anorexia (41.7%) and jaundice (25.0%). Tumors were located at pancreatic head in 5 (41.7%) patients, tail in 5 (41.7%), and body in 4 (33.3%). Median tumor size was 6.3 cm. Surgical resection was performed on 7 patients, bypass surgery on 3, and exploratory laparotomy with biopsy on 2. No surgical mortality was identified. Seven (58.3%) and 11 (91.7%) patients died within 6 and 12 months of operation, respectively. Median survival of 12 patients was 4.41 months. Seven patients receiving surgical resection had median survival of 6.51 months. Patients with stage IIB pancreatic ASC had shorter median survival compared to those with adenocarcinoma.

Conclusion
Aggressive surgical management does not appear effective in treating pancreatic ASC patients. Strategies involving non-surgical treatment such as chemotherapy, radiotherapy or target agents should be tested.
Simultaneous circulation of genotypes I and III of dengue virus 3 in Colombia
Authors: Usme-Ciro Jose A , Mendez Jairo A , Tenorio Antonio , Rey Gloria J , Domingo Cristina , Gallego-Gomez Juan C 
Published: September 2008

Abstract

Background
Dengue is a major health problem in tropical and subtropical regions. In Colombia, dengue viruses (DENV) cause about 50,000 cases annually, 10% of which involve Dengue Haemorrhagic Fever/Dengue Shock Syndrome. The picture is similar in other surrounding countries in the Americas, with recent outbreaks of severe disease, mostly associated with DENV serotype 3, strains of the Indian genotype, introduced into the Americas in 1994.

Results
The analysis of the 3'end (224 bp) of the envelope gene from 32 DENV-3 strains recently recovered in Colombia confirms the circulation of the Indian genotype, and surprisingly the co-circulation of an Asian-Pacific genotype only recently described in the Americas.

Conclusion
These results have important implications for epidemiology and surveillance of DENV infection in Central and South America. Molecular surveillance of the DENV genotypes infecting humans could be a very valuable tool for controlling/mitigating the impact of the DENV infection.
Multicystic urothelial carcinoma of the bladder with gland-like lumina and with signet-ring cells. A case report
Authors: Alvarado-Cabrero Isabel , Pérez-Montiel Delia , Hes Ondrej 
Published: September 2008

Abstract
We present the case of 80-year-old male with superficial papillary urothelial carcinoma of the urinary bladder with striking multicystic architecture with a combination of features of urothelial carcinoma with gland-like lumina, with signet-ring cell differentiation and microcystic pattern. However, the tumor shared the morphologic features of several variants of urothelial carcinoma, the most important differential diagnosis covered so-called florid Brunneriosis, cystitis cystica, and primary adenocarcinomas of the urinary bladder.
Bacterial infection alters the kinetics and function of iNKT cell responses
Authors: Choi Hak-Jong , Xu Honglin , Geng Yanbiao , Colmone Angela , Cho Hoonsik , Wang Chyung-Ru 
Published: September 2008

AbstractCD1d-restricted Vα14 invariant NKT cells (iNKT) are innate-like, immunoregulatory lymphocytes that play critical roles in autoimmunity, tumor surveillance, and infectious disease. Although iNKT cells are activated during microbial infection, the impacts of infection on the function of iNKT cells have not been fully characterized. Using a Listeria monocytogenes (LM) infection model, we found that iNKT cells failed to expand after infection, resulting in prolonged loss in the spleen, in contrast to the typical expansion and contraction of conventional T cells. iNKT cells from LM-infected mice responded more rapidly to secondary LM infection; however, they became functionally hyporesponsive to antigenic challenge for at least 1 month. This infection-induced hyporesponsiveness was also induced by Mycobacteria infection and was more profound in LM-infected, thymectomized mice, suggesting that infection-primed iNKT cells might have altered functionality. Interestingly, activation with α-galactosylceramide-loaded dendritic cells was able to overcome infection-induced hyporesponsiveness of iNKT cells, suggesting a role for extrinsic factors in this functional deficit. Taken together, these findings suggest that infection affects iNKT cell responses quantitatively and qualitatively. As humans are under constant microbial insult, predictions of iNKT cell function based on naïve animal models may not accurately reflect iNKT cell behavior in a clinical setting.
Regulation of WAVE1 expression in macrophages at multiple levels
Authors: Dinh Hang , Scholz Glen M , Hamilton John A 
Published: September 2008

AbstractM-CSF (or CSF-1) controls macrophage lineage development and function. A CSF-1-dependent culture system was established, which monitored the differentiation of CSF-1-responsive macrophage populations over time and upon adherence. Wiskott-Aldrich syndrome protein verprolin homologous (WAVE) proteins are involved in actin reorganization, a process critical to many cell functions. WAVE2 but not WAVE1 has been considered significant for macrophage function. Using the CSF-1-dependent differentiation system, we were able to demonstrate the contrasting regulation of the expression of WAVE1 and WAVE2; the levels of the latter rose over time and as the macrophage population became adherent, although those of the former increased over time but were down-regulated upon adherence. Evidence was obtained that WAVE1 was also cleaved to a novel, 60-kDa fragment by macrophage adherence and by another pathway involving calpain-mediated proteolysis. Mutagenesis studies indicated that cleavage of WAVE1 by calpain results in the removal of the verprolin-homology, cofilin-like, and acidic domain and thus, the loss of WAVE1 activity. We suggest that WAVE1 is also important for macrophage biology and that it could have separate functions to those of WAVE2.
Comparison of Referring and Final Pathology for Patients With Non-Hodgkin's Lymphoma in the National Comprehensive Cancer Network
Authors: LaCasce Ann S. , Kho Michelle E. , Friedberg Jonathan W. , Niland Joyce C. , Abel Gregory A. , Rodriguez Maria Alma , Czuczman Myron S. , Millenson Michael M. , Zelenetz Andrew D. , Weeks Jane C. 
Published: September 2008

Purpose Before the implementation of the WHO lymphoma classification system, disagreement about pathologic diagnosis was common. We sought to estimate the impact of expert review in the modern era by comparing final pathologic diagnoses at five comprehensive cancer centers with diagnoses assigned at referring centers. Patients and Methods Patients in the National Comprehensive Cancer Network (NCCN) non-Hodgkin's lymphoma (NHL) database with a documented pathologic diagnosis before presentation and a final pathologic diagnosis of any of five common B-cell NHLs were eligible. After central review of discordant cases, we estimated the rate of pathologic concordance, then investigated the etiology of discordance as well its potential impact on prognosis and treatment. Results The overall pathologic discordance rate was 6% (43 of 731 patients; 95% CI, 4% to 8%). For the majority of cases in which the referring diagnosis was apparently final, no additional studies were conducted at the NCCN center, and the change in diagnosis reflected a different interpretation of existing data. Concordance was highest for diffuse large B-cell lymphoma (95%) and follicular lymphoma (FL; grades 1, 2, and not otherwise specified, 95%) and lowest for grade 3 FL (88%). Of the 43 pathologically discordant cases, 81% (35 patients) might have experienced a change in treatment as a result of the pathologic reclassification. Conclusion In the era of the WHO lymphoma classification system, the majority of common B-cell NHLs diagnosed in the community were unchanged by second opinion review by an expert hematopathologist. However, for one patient in 20, there was a discordance in diagnosis that could have altered therapy.
Different Outcomes of Unliganded and Liganded Estrogen Receptor-α on Neurite Outgrowth in PC12 Cells
Authors: Mérot Yohann , Ferrière François , Gailhouste Luc , Huet Guillaume , Percevault Frédéric , Saligaut Christian , Flouriot Gilles 
Published: September 2008

A precise description of the mechanisms by which estrogen receptor-α (ERα) exerts its influences on cellular growth and differentiation is still pending. Here, we report that the differentiation of PC12 cells is profoundly affected by ERα. Importantly, depending upon its binding to 17β-estradiol (17βE2), ERα is found to exert different effects on pathways involved in nerve growth factor (NGF) signaling. Indeed, upon its stable expression in PC12 cells, unliganded ERα is able to partially inhibit the neurite outgrowth induced by NGF. This process involves a repression of MAPK and phosphatidylinositol 3-kinase/Akt signaling pathways, which leads to a negative regulation of markers of neuronal differentiation such as VGF and NFLc. This repressive action of unliganded ERα is mediated by its D domain and does not involve its transactivation and DNA-binding domains, thereby suggesting that direct transcriptional activity of ERα is not required. In contrast with this repressive action occurring in the absence of 17βE2, the expression of ERα in PC12 cells allows 17βE2 to potentiate the NGF-induced neurite outgrowth. Importantly, 17βE2 has no impact on NGF-induced activity of MAPK and Akt signaling pathways. The mechanisms engaged by liganded ERα are thus unlikely to rely on an antagonism of the inhibition mediated by the unliganded ERα. Furthermore, 17βE2 enhances NGF-induced response of VGF and NFLc neuronal markers in PC12 clones expressing ERα. This stimulatory effect of 17βE2 requires the transactivation functions of ERα and its D domain, suggesting that an estrogen-responsive element-independent transcriptional mechanism is potentially relevant for the neuritogenic properties of 17βE2 in ERα-expressing PC12 cells.In the absence of its ligand, ERα partially inhibits the nerve growth factor-induced neurite outgrowth of PC12 cells, whereas, once liganded, it enhances differentiation.