bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulation and homing of melanoma‐reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte‐derived dendritic cells
Authors: Berger Thomas G. , Haendle Ina , Schrama David , Lüftl Matthias , Bauer Nicolas , Pedersen Lars Østergaard , Schuler‐Thurner Beatrice , Hohenberger Werner , Straten Per thor , Schuler Gerold , Becker Jürgen C. 
Published: June 2004

AbstractAnticancer immune therapies aim at the induction of tumor‐specific T cells, which ultimately should kill tumor cells. The effector cells should, therefore, not only exert cytotoxic activity but also home to and infiltrate the tumor site. Hence, monitoring of immune modulating therapies should not be restricted to the circulating pool of peripheral blood mononuclear cells (PBMC) but also include tumor‐infiltrating lymphocytes (TIL), as well as the correlation of these findings to the clinical course. We report here on the longitudinal immunologic workup of a melanoma patient who developed remarkably potent ex vivo detectable antimelanoma cytotoxic T‐cell (CTL) responses after vaccinations with autologous peptide‐pulsed dendritic cells. Such potent CTL responses to multiple tumor antigens have, to the best of our knowledge, not been described previously in melanoma patients, neither spontaneously nor after any therapy. This patient first experienced a transient response to therapy but finally succumbed to disease progression and died. Progression was associated with the decline of the numbers of tumor‐reactive T cells in circulation and at skin metastases in addition to the loss of MHC class I antigens. The immunologic analysis revealed that fully functional tumor‐specific T cells were present in the peripheral blood of this patient during the phase of a relatively stable disease, and in situ tetramer staining demonstrated that these cells were also accumulated at cutaneous and visceral tumor sites. Furthermore, comparative clonotype mapping of PBMC and TIL depicted an overlapping TCR repertoire usage among these 2 compartments. Since strong CTL responses as observed in this patient are the goal of cancer vaccination but are so far only rarely observed, the thorough analysis of patients exhibiting either exceptional clinical and/or immunologic responses appears critical to understanding how vaccine therapies work and can be further improved. © 2004 Wiley‐Liss, Inc.
Against which human papillomavirus types shall we vaccinate and screen? the international perspective
Authors: Muñoz Nubia , Bosch F. Xavier , Castellsagué Xavier , Díaz Mireia , de Sanjose Silvia , Hammouda Doudja , Shah Keerti V. , Meijer Chris J.L.M. 
Published: June 2004

AbstractAt least 15 types of HPV have been associated with cervical cancer, but current HPV vaccines confer only type‐specific immunity. To determine geographic variations in the HPV type distribution in cervical cancer, we carried out a pooled analysis of data from an international survey of HPV types in cervical cancer and from a multicenter case‐control study, both co‐coordinated by the IARC. Study cases were 3,607 women with incident, histologically confirmed cervical cancer recruited in 25 countries. HPV DNA detection and typing in cervical cells or biopsies were centrally done using PCR assays. Estimates of the potential number of cases prevented by HPV type‐specific vaccines and changes in the validity of different HPV screening cocktails were calculated. HPV DNA was detected in 96% of specimens, and 30 different types were detected. The 15 most common types were, in descending order of frequency, 16, 18, 45, 31, 33, 52, 58, 35, 59, 56, 39, 51, 73, 68 and 66. Higher than average proportions of type 16 were found in northern Africa, of type 18 in south Asia, of type 45 in sub‐Saharan Africa and of type 31 in Central/South America. A vaccine including types 16 and 18 could potentially prevent 71% of cervical cancers worldwide, but its impact with regard to the percentage of cases potentially prevented would be higher in Asia and Europe/North America. In contrast, a vaccine containing the 7 most common HPV types would prevent about 87% of cervical cancers worldwide, with little regional variation. The impact of modifying the number of types in the screening cocktail tests would be small and probably irrelevant for screening programs. © 2004 Wiley‐Liss, Inc.
Suppression of cyclooxygenase‐2 overexpression by 15S‐hydroxyeicosatrienoic acid in androgen‐dependent prostatic adenocarcinoma cells
Authors: Pham Hung , Banerjee Tinku , Ziboh Vincent A. 
Published: June 2004

AbstractEmerging reports now implicate alterations of arachidonic acid (AA) metabolism with prostate carcinogenesis. To test this hypothesis, androgen‐primed benign hyperplastic (BHC) and malignant tumorigenic (MTC) cells derived from the Lobund‐Wistar rat model of autochthonous prostate adenocarcinoma were incubated with 14C‐AA. Our data using MTCs revealed enhanced dual metabolism of 14C‐AA via COX to generate increased PGE2 and via 5‐lipoxygenase (LOX) to generate increased 5S‐HETE in tumorigenic cells. Western blot of MTCs revealed upregulation of COX‐2 expression. This paralleled the increased biosynthesis of PGE2. Since some polyunsaturated fatty acids have been reported to modulate AA metabolism and tumorigenesis, we primed the cells with either γ‐linolenic acid (GLA) or its in vivo metabolite, 15S‐HETrE, prior to incubation with AA. Our data revealed suppression of COX‐2 expression/PGE2 biosynthesis. In parallel, priming cells with 15S‐HETrE resulted in greater suppression of COX‐2 expression/PGE2 biosynthesis. These findings suggest that 15S‐HETrE could function in vivo after dietary intake of GLA to suppress DHT‐enhanced prostatic COX‐2 expression/PGE2 biosynthesis and, thus, alleviate tumor growth and progression. © 2004 Wiley‐Liss, Inc.
Differential expression of 9‐O‐acetylated sialoglycoconjugates on leukemic blasts: A potential tool for long‐term monitoring of children with acute lymphoblastic leukemia
Authors: Pal Santanu , Ghosh Shyamasree , Bandyopadhyay Suman , Mandal Chhabinath , Bandhyopadhyay Santu , Kumar Bhattacharya Dilip , Mandal Chitra 
Published: June 2004

AbstractEarlier studies have demonstrated overexpression of 9‐O‐acetylated sialoglycoconjugates (9‐O‐AcSGs) on lymphoblasts, concomitant with high titers of anti‐9‐O‐AcSG antibodies in childhood acute lymphoblastic leukemia (ALL). Our aim was to evaluate the correlation between expression of different 9‐O‐AcSGs during chemotherapeutic treatment. Accordingly, expression of 9‐O‐AcSGs on lymphoblasts of ALL patients (n = 70) were longitudinally monitored for 6 years (1997–2002), using Achatinin‐H, a 9‐O‐acetylated sialic acid (9‐O‐AcSA) binding lectin with preferential affinity for 9‐O‐AcSGs with terminal 9‐O‐AcSAα2→6GalNAc. Western blot analysis of patients (n = 30) showed that 3 ALL‐specific 9‐O‐AcSGs (90, 120 and 135 kDa) were induced at presentation; all these bands disappeared after treatment in patients (n = 22) who had disease‐free survival. The 90 kDa band persisted in 8 patients who subsequently relapsed with reexpression of the 120 kDa band. FACS analysis revealed that at presentation (n = 70) 90.1 ± 5.0% cells expressed 9‐O‐AcSGs, which decreased progressively with chemotherapy, remained <5% during clinical remission and reappeared in relapse (80 ± 10%, n = 18). Early clearance of 9‐O‐AcSG+ cells, during 4–8 weeks of treatment showed a good correlation with low risk of relapse. Sensitivity of detection of 9‐O‐AcSG+ cells was 0.1%. Numbers of both high‐ and low‐affinity binding sites were maximum at presentation, decreased with treatment and increased again in clinical relapse. We propose that close monitoring of 90 and 120 kDa 9‐O‐AcSGs may serve as a reliable index for long‐term management of childhood ALL and merits therapeutic consideration. © 2004 Wiley‐Liss, Inc.
Algorithms based on prostate‐specific antigen (PSA), free PSA, digital rectal examination and prostate volume reduce false‐postitive PSA results in prostate cancer screening
Authors: Finne Patrik , Finne Ralf , Bangma Chris , Hugosson Jonas , Hakama Matti , Auvinen Anssi , Stenman Ulf‐Håkan 
Published: June 2004

AbstractOur objective was to determine whether multivariate algorithms based on serum total PSA, the free proportion of PSA, age, digital rectal examination and prostate volume can reduce the rate of false‐positive PSA results in prostate cancer screening more effectively than the proportion of free PSA alone at 95% sensitivity. A total of 1,775 consecutive 55‐ to 67‐year‐old men with a serum PSA of 4–10 μg/l in the European Randomized Study of Screening for Prostate Cancer were included. To predict the presence of cancer, multivariate algorithms were constructed using logistic regression (LR) and a multilayer perceptron neural network with Bayesian regularization (BR‐MLP). A prospective setting was simulated by dividing the data set chronologically into one set for training and validation (67%, n = 1,183) and one test set (33%, n = 592). The diagnostic models were calibrated using the training set to obtain 95% sensitivity. When applied to the test set, the LR model, the BR‐MLP model and the proportion of free PSA reached 92%, 87% and 94% sensitivity and reduced 29%, 36% and 22% of the false‐positive PSA results, respectively. At a fixed sensitivity of 95% in the test set, the LR model eliminated more false‐positive PSA results (22%) than the proportion of free PSA alone (17%) (p < 0.001), whereas the BR‐MLP model did not (19%) (p = 0.178). The area under the ROC curve was larger for the LR model (0.764, p = 0.030) and the BR‐MLP model (0.760, p = 0.049) than for the proportion of free PSA (0.718). A multivariate algorithm can be used to reduce unnecessary prostate biopsies in screening more effectively than the proportion of free PSA alone, but the algorithms will require updating when clinical practice develops with time. © 2004 Wiley‐Liss, Inc.
PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's disease
Authors: Matsumura Yasuhiro , Matsumura Yumi , Nishigori Chikako , Horio Takeshi , Miyachi Yoshiki 
Published: June 2004

AbstractTo identify cancer‐related genes that are involved in the carcinogenesis of extramammary Paget's disease (EMPD), we compared mRNA expression profiles of EMPD lesions and corresponding normal skin using cDNA array. Sixty‐eight genes were highly expressed (>5‐fold) in EMPD lesions compared to normal skin, and 40 genes were expressed less than one‐fifth in EMPD lesions. Among them, PIG7/LITAF mRNA was overexpressed in 3 of 4 EMPD cases. PIG7/LITAF transcription is induced by p53 expression and has been implicated in the p53‐induced apoptotic pathway. Since expression of p53 mRNA and p53 protein was not high in any of the 3 EMPD samples compared to the intact skin of the same patient, we analyzed PIG7/LITAF cDNA mutations among 12 EMPD samples (including the former 4) by PCR‐SSCP. Three samples showed shifted bands (2 had point mutations leading to amino acid substitutions and 1 had a silent mutation). One sample with amino acid substitution overexpressed PIG7/LITAF mRNA in cDNA array analysis and RT‐PCR. PIG7/LITAF mRNA expression is confined to tumor cells in in situ mRNA hybridization analysis. These results indicate that genetic disorder and overexpression of PIG7/LITAF may be involved in EMPD carcinogenesis. © 2004 Wiley‐Liss, Inc.
Insulin‐like growth factor (IGF)‐I and IGF‐binding protein 3 and the risk of premenopausal breast cancer: A meta‐analysis of literature
Authors: Sugumar Aravind , Liu Yen‐Chun , Xia Qiang , Koh Yea‐Suk , Matsuo Keitaro 
Published: June 2004

AbstractBiologic evidence suggests substantial effect of insulin‐like growth factor (IGF)‐I in mammary cell carcinogenesis. However, controversy remains regarding the association between circulating IGF‐I levels and the risk of premenopausal breast cancer in epidemiologic studies. In addition, the association of IGF‐binding protein (IGFBP)‐3, which binds with and modifies the effect of IGF‐I, is unclear. To clarify these associations, we performed a meta‐analysis of all the published studies. A systematic review of literature was conducted. Eligible study designs were nested case‐control and population‐based case‐control studies that give estimates for menopausal women. The studies published between January 1990 and March 2003 were obtained from Medline. We obtained 7 studies, consisting of 688 premenopausal incident breast cancer cases and 1,366 controls, for our final evaluation. Summary statistics were odds ratios (ORs) comparing the highest and the lowest levels of IGF‐I and IGFBP‐3 adjusted for confounders other than IGF‐I or IGFBP‐3. There was neither evidence of heterogeneity between studies nor evidence of publication bias. The confounders considered and the contrast used for the ORs were the major source of variation. The subjects with higher circulating levels of IGF‐I had marginally significant increased risk of breast cancer with an OR of 1.74 (95% CI = 0.97–3.13; p = 0.06). No significant difference was observed for IGFBP‐3 group (OR = 1.60; 95% CI = 0.84–3.02; p = 0.15). In conclusion, we found a marginally significant association between circulating IGF‐I levels and the risk of premenopausal breast cancer. © 2004 Wiley‐Liss, Inc.
Risk of esophageal, ovarian, testicular, kidney and bladder cancers and leukemia among finnish workers exposed to diesel or gasoline engine exhaust
Authors: Guo Johannes , Kauppinen Timo , Kyyrönen Pentti , Heikkilä Pirjo , Lindbohm Marja‐Liisa , Pukkala Eero 
Published: June 2004

AbstractOccupational exposure to diesel exhaust has been classified as probably carcinogenic and that to gasoline engine exhaust as possibly carcinogenic to humans. Earlier results concerning cancers other than lung cancer are scarce and inconsistent, and exposure‐response relations have seldom been reported. We followed up a cohort of all economically active Finns born between 1906 and 1945 for 30 million person‐years during 1971–1995. Incident cases of esophageal cancer (n = 2,198), ovarian cancer (5,082), testicular cancer (387), kidney cancer (7,366), bladder cancer (8,110) and leukemia (4,562) were identified through a record linkage with the Finnish Cancer Registry. Occupations from the population census in 1970 were converted to exposures to diesel and gasoline engine exhausts with a job‐exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as product of prevalence, level and estimated duration of exposure. The relative risk (RR) of cancer for exposure categories in relation to the unexposed group was calculated using the Poisson regression model and adjusted for confounders. An increasing RR for ovarian cancer was observed with the increasing CE of diesel exhaust (p for trend = 0.006). The RR in the highest CE category was 3.69 (95% CI = 1.38–9.86). For gasoline engine exhaust, the RR was significantly increased only in the middle CE category (1.70; 95% CI = 1.11–2.62). Slight elevations of RR for bladder and kidney cancers were found at the lowest exposure level of engine exhausts, largely attributable to drivers. No effect of the exposures was observed for the other cancers. This study suggests an exposure‐response relation between diesel exhaust and ovarian cancer. © 2004 Wiley‐Liss, Inc.
Effect of titanium surface topography on macrophage activation and secretion of proinflammatory cytokines and chemokines
Authors: Refai Ali K. , Textor Marcus , Brunette Donald M. , Waterfield J. Douglas 
Published: June 2004

AbstractThe macrophage has a major role in normal wound healing and the reparative process around implants. Murine macrophage‐like cells RAW 264.7 were used to investigate the effect of titanium surfaces on macrophage activation and secretion of proinflammatory cytokines [interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α] and chemokines (monocyte chemoattractant protein‐1 and macrophage inflammatory protein‐1α). Four topographies were used: those produced by mechanically polishing, coarse sand blasting, acid etching, and sandblasting and acid etching (SLA). Macrophages were plated on the four titanium surfaces at a population density of 5 × 105 cells/mL/well. Tissue culture plastic and tissue culture plastic plus lipopolysaccharide (LPS) served as negative and positive control, respectively. In addition, all surfaces were tested for their effects on macrophages in the presence of LPS. Supernatants were collected for assays after 6, 24, and 48 h and the numbers of macrophages attached to the surfaces were quantified using the DAPI (4,6‐di‐amidino‐2‐phenylindole) assay. Cytokine and chemokine levels were measured with sandwich enzyme‐linked immunosorbent assays. Statistical comparison between the surfaces and the controls was determined by using the two‐way analysis of variance including interaction effect (two tailed and p ≤ 0.05). Unstimulated macrophages increased their secretion of the proinflammatory cytokine (TNF‐α) when attached to rough surfaces (acid etching and SLA, p ≤ 0.05). In macrophages stimulated with LPS, the roughest surface SLA produced higher levels of IL‐1β, IL‐6, and TNF‐α at 24 and 48 h than all other surfaces (p ≤ 0.05). Surface topography also modulated the secretion of the chemokines monocyte chemoattractant protein‐1 and macrophage inflammatory protein‐1α by macrophages. Unstimulated macrophages attached to the SLA surface down‐regulated their production of chemokines (p ≤ 0.05) whereas LPS‐stimulated macrophages attached to the SLA surface up‐regulated their production (p ≤ 0.05). Moreover, the SLA surface was found to act synergistically with LPS as well as the combination of blasting and etching features of the SLA surface resulted in significant release of proinflammatory cytokines and chemokines by stimulated macrophages at 24 and 48 h (p ≤ 0.05). This in vitro study has demonstrated that surface topography, in particular the SLA surface, modulated expression of proinflammatory cytokines and chemokines by macrophages in a time‐dependent manner. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 194–205, 2004
Apatite formation in the reaction‐setting mixture of Ca(OH)2KH2PO4 system
Authors: Fadeeva Inna V. , Barinov Sergey M. , Komlev Vladimir S. , Fedotov Denis A. , Ďurišin Juraj , Medvecky Lubomir 
Published: June 2004

AbstractDevelopment of a new calcium phosphate cement (CPC) system as an alternative to that commonly used, basically consisting of tetracalcium phosphate and dicalcium phosphate self‐setting mixtures, could be of interest in achieving special properties of the product. Powder mixtures of Ca(OH)2 and KH2PO4 were studied to assess their potential for the precipitation of apatite‐like phase with the use of potassium phosphate salt solution as the cement liquid. X‐ray diffraction and infrared (IR) spectroscopy studies and pH and setting time measurements were performed. The set cement was revealed to consist of a low crystalline carbonate‐substituted apatite‐like phase. The setting time of the cement was about 5 min. Its dissolution in distilled water led to an increase in solution pH to about 11.5, the pH slowly decreasing to 10.2 at day 10. The results showed the cement to be of an increased carbonate substitution ability compared to the tetracalcium phosphate–dicalcium phosphate anhydrous cement. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 303–308, 2004
Emerging non‐apoptotic functions of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)/Apo2L
Authors: Pietro Roberta Di , Zauli Giorgio 
Published: June 2004

AbstractTumor necrosis factor (TNF) is a cytokine that mediates tumor necrosis. To date, 20 different members of the TNF super‐family and 21 different receptors have been identified. All ligands of the TNF super‐family have been found to activate transcription factor NF‐κB and c‐Jun kinase. Members of this family have diverse biological effects, including induction of apoptosis, promotion of cell survival, and regulation of the immune system and hematopoiesis. The current review focuses on the biological effects of TNF‐related apoptosis‐inducing ligand (TRAIL), a TNF super‐family member which, a few years ago, generated considerable enthusiasm for its anticancer activity, not accompanied by general toxicity in most normal tissues and organs. © 2004 Wiley‐Liss, Inc.
Non‐apoptotic desquamation of cells from corneal epithelium: Putative role for Muc4/sialomucin complex in cell release and survival
Authors: Lomako Joseph , Lomako Wieslawa M. , Decker Susan J. , Carraway Coralie A. Carothers , Carraway Kermit L. 
Published: June 2004

AbstractMuc4/sialomucin complex (SMC), a large heterodimeric mucin composed of an extracellular mucin subunit ASGP‐1 and a transmembrane subunit ASGP‐2, is present at the rat ocular surface localized mainly to the most superficial layers of the epithelia. To investigate corneal homeostasis and the functions of Muc4/SMC at the ocular surface, we developed a corneal epithelial cell culture system from corneal explants, from which migrating cells formed an epithelial sheet resembling the native epithelium with regard to microanatomy, expression of characteristic markers, cell migration, and Muc4/SMC expression. Cells migrating from the explants expressed smooth muscle actin. Proliferation was detected only on the edge of epithelial sheet in the immature epithelium and throughout the sheet in confluent cultures. Microscopy revealed that the epithelial sheet was formed from four to six layers of cells expressing keratin 3 and Muc4/SMC in forms identical to those expressed at ocular surface in vivo. Electron microscopy showed cells in various morphological states in the process of releasing from the surface of the multilayer (desquamating). Surprisingly, few of these cells showed evidence of apoptosis, either by morphological or DNA fragmentation analyses. These results suggest a new model for desquamation from stratified epithelia, in which desquamation and apoptosis are independent and sequential processes. Desquamating cells also exhibit a high level of Muc4/SMC. Since Muc4/SMC has been shown to be a potent anti‐adhesive and a repressor of apoptosis, we propose that it plays a role in the non‐apoptotic desquamation process. © 2005 Wiley‐Liss, Inc.
Heterogeneity between hippocampal and septal astroglia as a contributing factor to differential in vivo AMPA excitotoxicity
Authors: Rodríguez Manuel J. , Martínez‐Sánchez Mónica , Bernal Fabián , Mahy Nicole 
Published: June 2004

AbstractAstroglial participation in the regional differences of vulnerability to α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐induced neurodegeneration was investigated in the rat hippocampus and medial septum using L‐α‐aminoadipate (α‐AA) as a specific astroglial toxin. α‐AA was microinjected in the hippocampus and the medial septum and a time‐course study was carried out between 2 hr and 3 days. When compared to controls, microinjection of α‐AA in the hippocampus induced within 3 days a reversible loss of glial fibrillary acidic protein (GFAP) immunostaining and a microglial reaction without any neuronal loss, whereas in the medial septum it caused no effects on astroglial, microglial, or neuronal populations. Differences in hippocampus and medial septum vulnerability were also evidenced when α‐AA was co‐injected with AMPA and neurodegeneration was assessed in terms of neuronal loss, glial reactions, calcification, and atrophy of the area. In the hippocampus, α‐AA increased AMPA excitotoxicity with marked disorganization of all hippocampal subfields, increased neuronal loss, a more important astroglial reaction, a larger area of microgliosis, and a greater abundance of calcium deposits. By contrast, in the medial septum α‐AA did not modify any parameter of the AMPA‐induced lesion. In conclusion, the presence of different astroglial populations in hippocampus and medial septum results in a different participation to AMPA excitotoxicity that may determine, at least in part, the specific regional vulnerability to neurodegeneration. © 2004 Wiley‐Liss, Inc.