bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gonadotropin‐releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma
Authors: Recchia Francesco , Saggio Gaetano , Amiconi Giovanna , Blasio Anna Di , Cesta Alisia , Candeloro Giampiero , Rea Silvio 
Published: December 2005

AbstractBACKGROUNDThe objective of the current study was a retrospective evaluation of 100 consecutive premenopausal women with high‐risk, early breast carcinoma who received a gonadotropin‐releasing hormone (Gn‐RH) analogue as ovarian protection during adjuvant chemotherapy.METHODSAfter surgery, patients received a Gn‐RH analogue and adjuvant chemotherapy, which was tailored to their peculiar biologic features. The median patient age was 43 years (range, 27–50 yrs). Fifty‐two women had positive estrogen receptor (ER) status, and 48 women had negative ER status. There were 64 women with Stage II breast carcinoma and 36 women with UICC Stage III breast carcinoma. All patients had their serum estradiol suppressed to values < 40 pg/mL. The chemotherapy regimens administered included cyclophosphamide, methotrexate, and 5‐fluorouracil (n = 26 patients) and anthracycline‐based regimens (n = 74 patients, including 9 patients who had > 10 positive axillary lymph nodes, who also received high‐dose chemotherapy with autologous peripheral blood progenitor cell transplantation). Patients with positive c‐erb‐2 status also received a taxane. Eighty patients received radiation therapy. During therapy with the Gn‐RH analogue, patients who had a positive ER status after chemotherapy received an aromatase inhibitor.RESULTSAfter a median follow‐up of 75 months, normal menses were resumed by all patients younger than age 40 years and by 56% of patients older than age 40 years. Three pregnancies were observed that resulted in two normal deliveries and one voluntary abortion. The projected recurrence‐free survival rates at 5 years and 10 years were 84% and 76%, respectively; and the projected overall survival rates at 5 years and 10 years were 96% and 91%, respectively.CONCLUSIONSThe current data showed that, in premenopausal women with early breast carcinoma, the addition of a Gn‐RH analogue to adjuvant therapy and temporary total estrogen suppression in patients with ER‐positive disease was tolerated well, protected long‐term ovarian function, and appeared to improve the expected clinical outcome. Cancer 2006. © 2005 American Cancer Society.
Racial/ethnic patterns in lifetime and age‐conditional risk estimates for selected cancers
Authors: Miller Barry A. , Scoppa Steven M. , Feuer Eric J. 
Published: December 2005

AbstractBACKGROUNDEstimates of the probability of developing or dying from cancer, either over a lifetime or over a specified number of years, are useful summary measures of the burden of cancer in a population.METHODSThe authors used publicly available DevCan software and new, detailed, racial/ethnic data bases that were developed in the Surveillance Research Program of the National Cancer Institute to produce risk estimates for selected major cancers among American Indian/Aleut/Eskimo, black, Chinese, Filipino, native Hawaiian, Japanese, white (total, non‐Hispanic), and Hispanic populations.RESULTSJapanese and non‐Hispanic white men had the highest lifetime risk for developing cancer (47.94% and 47.41%, respectively), and the American Indian/Eskimo/Aleut population (excluding Alaska) had the lowest lifetime risk among men (24.30%). Among women, white and American Indian/Eskimo/Aleut (in Alaska) populations had higher lifetime risks than Japanese women, whereas American Indian/Eskimo/Aleut (excluding Alaska) women had the lowest risk. The age‐conditional probabilities of developing cancer within the next 10 years among men and women age 60 years and the lifetime probabilities of dying from cancer also were reported by racial/ethnic group.CONCLUSIONSRacial/ethnic disparities in the lifetime risk of cancer may be because of differences in cancer incidence rates, but they also may reflect differential mortality rates from causes other than the cancer of interest. Furthermore, because cross‐sectional incidence and mortality rates are used in calculating the DevCan lifetime risk estimates, results must be interpreted with caution when events, such as the widespread and rapid implementation of a new screening test, are known to have influenced disease rates. Cancer 2006. © 2005 American Cancer Society.
Elevated serum heparanase‐1 levels in patients with pancreatic carcinoma are associated with poor survival
Authors: Quiros Roderick M. , Rao Geetha , Plate Janet , Harris Jules E. , Brunn Gregory J. , Platt Jeffrey L. , Gattuso Paolo , Prinz Richard A. , Xu Xiulong 
Published: December 2005

AbstractBACKGROUNDIt has previously been shown that heparanase‐1 (HPR1), an endoglycosidase, is up‐regulated in pancreatic carcinoma. The purpose of this study was to test whether serum HPR1 levels in pancreatic carcinoma patients are elevated, and whether higher serum HPR1 levels are associated with a shortened survival.METHODSSerum HPR1 levels in 40 healthy donors, 31 pancreatic carcinoma patients, and 11 patients treated with gemcitabine were measured by a novel enzyme‐linked immunoadsorbent assay. HPR1 expression in tumors was analyzed by immunohistochemical staining. Patient overall survival time was determined according to the Kaplan–Meier method, and their difference was evaluated by the log‐rank test. A P value < 0.05 was considered statistically significant.RESULTSThe mean serum HPR1 activity in pancreatic carcinoma patients was 439 ± 14 units/mL, compared with 190 ± 4 units/mL in the control serum samples from healthy donors. Serum HPR1 levels were significantly higher in patients with HPR1‐positive tumors (660 ± 62 units/mL) compared with those with HPR1‐negative tumors (241 ± 14 units/mL). The mean survival of 19 pancreatic carcinoma patients with serum HPR1 activity > 300 units/mL was 7.9 ± 0.2 months, whereas the mean survival of 12 patients with serum HPR1 activity < 300 units/mL was 13.3 ± 0.6 months. A Kaplan–Meier plot of the patient survival curve followed by log‐rank test revealed that patients in the high serum HPR1 group had a significantly shorter survival compared with those in the low serum HPR1 group. Mean serum HPR1 activity decreased by 64% in 11 pancreatic carcinoma patients after 2 weeks of treatment with gemcitabine.CONCLUSIONSSerum HPR1 activity in pancreatic carcinoma patients was found to be significantly elevated, in particular in those with HPR1‐positive tumors. Increased serum HPR1 activity was associated with a shorter survival in patients with pancreatic carcinoma patients. Cancer 2006. © 2005 American Cancer Society.
Solid tumors “melt” from the inside after successful CD8 T cell attack
Authors: Blohm Ulrike , Potthoff Dan , van der Kogel Albert J. , Pircher Hanspeter 
Published: December 2005

AbstractAdoptive transfer of tumor‐specific T cells represents a promising approach for cancer immunotherapy. Here, we visualized the anti‐tumor response of CD8 T cells from P14 TCR‐transgenic mice specific for the model antigen GP33 by immunohistology. P14 T cells, adoptively transferred into tumor‐bearing hosts, induced regression of established 3LL‐A9GP33 and MCA102GP33 tumors that express GP33 as a tumor‐associated model antigen. Strikingly, the visible effects of P14 T cell attack, such as the destruction of the tumor vasculature and accumulation of granulocytes, were predominantly detected inside the tumor mass. In regressing tumors, P14 T cells were found in the intact rim zone but not in central areas that were infiltrated with granulocytes and lacked CD31+ endothelial cells. The rim of P14 T cell‐treated tumors showed an increase in vascular density and decrease in hypoxia compared to untreated tumors. Hypoxic areas of tumors are known to exhibit decreased sensitivity to radiation therapy or chemotherapy. Thus, our data also imply that adoptive transfer of tumor‐specific CD8 T cells might synergize with radiation therapy or chemotherapy in the elimination of solid tumors in vivo.
Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine
Authors: García‐Piñeres Alfonso J. , Hildesheim Allan , Trivett Matthew , Williams Marcus , Wu Li , KewalRamani Vineet N. , Pinto Ligia A. 
Published: December 2005

AbstractDendritic cell‐specific intercellular adhesion molecule‐grabbing non‐integrin (DC‐SIGN), a specific C‐type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC‐SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus‐like particles (VLP) bind to DC‐SIGN expressed on transfected Raji cells and that antibodies against DC‐SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/chemokines. Although our results indicate that DC‐SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF‐α, IL‐6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC‐SIGN was blocked by anti‐DC‐SIGN antibodies. These results suggest that DC‐SIGN has a functional role in DC activation induced by HPV‐16 L1‐VLP, and thus highlight new aspects of DC interactions with HPV VLP.
Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy
Authors: Jakobsen Håvard , Hannesdottir Solveig , Bjarnarson Stefania P. , Schulz Dominique , Trannoy Emanuelle , Siegrist Claire‐Anne , Jonsdottir Ingileif 
Published: December 2005

AbstractImmunization with a tetanus‐protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1‐TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti‐PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1‐TT responded with proliferation and IFN‐γ secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2‐cytokine responses were observed in mice immunized with Pnc1‐TT. Impaired IFN‐γ production upon TT‐stimulation in vitro was also reflected in reduced IFN‐γ/IL‐5 ratio. The IL‐‐5 response correlated with IgG anti‐PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier‐specific IL‐5 production. These results show that immunization with Pnc1‐TT induces carrier‐specific T cell responses that increase with age and determine the levels of PPS‐specific Ab elicited. Whereas a weak and Th2‐biased response was observed in neonatal mice, infant mice showed a mixed Th1‐Th2 response as observed in adults.
Mechanism of pathogen‐specific TLR4 activation in the mucosa: Fimbriae, recognition receptors and adaptor protein selection
Authors: Fischer Hans , Yamamoto Masahiro , Akira Shizuo , Beutler Bruce , Svanborg Catharina 
Published: December 2005

AbstractThe mucosal host defence discriminates pathogens from commensals, and prevents infection while allowing the normal flora to persist. Paradoxically, Toll‐like receptors (TLR) control the mucosal defence against pathogens, even though the TLR recognise conserved molecules like LPS, which are shared between pathogens and commensals. This study proposes a mechanism of pathogen‐specific mucosal TLR4 activation, involving adhesive ligands and their host cell receptors. TLR4 signalling was activated in CD14‐negative, LPS‐unresponsive epithelial cells by P fimbriated, uropathogenic Escherichia coli but not by a mutant lacking fimbriae. Epithelial TLR4 signalling in vivo involved the glycosphingolipid receptors for P fimbriae and the adaptor proteins Toll/IL‐1R (TIR) domain‐containing adaptor inducing IFN‐β (TRIF)/TRIF‐related adaptor molecule (TRAM), but myeloid differentiation protein 88 (MyD88)/TIR domain‐containing adaptor protein were not required for the epithelial response. Substituting the P fimbriae with type 1 fimbriae changed TLR4 signalling from the TRIF to the MyD88 adaptor pathway. In addition, the adaptor proteins and the fimbrial type were found to influence bacterial clearance. Trif–/– and Tram–/– mice remained infected with P fimbriated E. coli but cleared the type 1 fimbriated strain, while Myd88–/– mice became carriers of both the P and the type 1 fimbriated bacteria. Thus, TLR4 may be engaged specifically by pathogens, when the proper cell surface receptors are engaged by virulence ligands.See accompanying commentary: http://dx.doi.org/10.1002/eji.200535777
HIV‐1 down‐regulates the expression of CD1d via Nef
Authors: Chen Nan , McCarthy Corinna , Drakesmith Hal , Li Demin , Cerundolo Vincenzo , McMichael Andrew J. , Screaton Gavin R. , Xu Xiao‐Ning 
Published: December 2005

AbstractHIV‐1 has evolved several strategies to subvert host immune responses to the infected cells. One is to inhibit CTL recognition by HIV‐1 Nef‐mediated down‐regulation of MHC‐I expression on the surface of infected cells. Here we report that Nef also reduces the expression of the non‐classical MHC‐I like CD1d molecule, a third lineage of antigen‐presenting molecule, which presents lipid antigens. Nef achieves this by increasing internalization of CD1d molecules from the cell surface and retaining CD1d in the trans‐Golgi‐network (TGN). This effect depends on a tyrosine‐based motif present in CD1 cytoplasmic tail as well as the actions of four Nef motifs, which are known to be involved in the down‐regulation of MHC‐I or CD4. These results suggest that Nef regulates intracellular trafficking of CD1d via a distinct but shared pathway with MHC‐I and CD4. Thus, HIV‐1 reduces the visibility of its infected cells not only to MHC‐I‐restricted T cells but also to CD1d‐restricted NKT cells. Given that CD1d‐restricted T cells have unique effector and regulatory functions in innate and adapted immune responses as compared with their counterpart MHC‐restricted T cells, our data provide additional new insights into molecular basis of HIV‐1‐mediated damage to the immune system.
Differential effects of the tryptophan metabolite3‐hydroxyanthranilic acid on the proliferation of human CD8+ T cells induced by TCR triggering or homeostatic cytokines
Authors: Weber Walter P. , Feder‐Mengus Chantal , Chiarugi Alberto , Rosenthal Rachel , Reschner Anca , Schumacher Reto , Zajac Paul , Misteli Heidi , Frey Daniel M. , Oertli Daniel , Heberer Michael , Spagnoli Giulio C. 
Published: December 2005

AbstractProduction of indoleamine 2,3‐dioxygenase (IDO) by tumor cells, leading to tryptophan depletion and production of immunosuppressive metabolites, may facilitate immune tolerance of cancer. IDO gene is also expressed in dendritic cells (DC) upon maturation induced by lipopolysaccarides or IFN. We investigated IDO gene expression in melanoma cell lines and clinical specimens as compared to mature DC (mDC). Furthermore, we explored effects of L‐kynurenine (L‐kyn) and 3‐hydroxyanthranilic acid (3‐HAA) on survival and antigen‐dependent and independent proliferation of CD8+ cells. We observed that IDO gene expression in cultured tumor cells and freshly excised samples is orders of magnitude lower than in mDC, providing highly efficient antigen presentation to CD8+ T cells. Non toxic concentrations of L‐kyn or 3‐HAA did not significantly inhibit antigen‐specific CTL responses. However, 3‐HAA, but not L‐kyn markedly inhibited antigen‐independent proliferation of CD8+ T cells induced by common receptor γ‐chain cytokines IL‐2, ‐7 and ‐15. Our data suggest that CD8+ T cell activation induced by antigenic stimulation, a function exquisitely fulfilled by mDC, is unaffected by tryptophan metabolites. Instead, in the absence of effective T cell receptor triggering, 3‐HAA profoundly affects homeostatic proliferation of CD8+ T cells.
A New Access to Enantiopure syn‐ and anti‐2‐Methyl‐1,3‐diol Moieties from Chiral Nonracemic α‐Bromo α′‐Sulfinyl Ketones Promoted by Samarium Diiodide
Authors: Colobert Françoise , Obringer Michel , Solladié Guy 
Published: December 2005

Abstractsyn‐ and anti‐2‐Methyl‐1,3‐diols have been prepared by a two‐step sequence that involves a SmI2‐promoted stereoselective Reformatsky addition of chiral nonracemic α‐bromo α′‐sulfinyl ketones to various aldehydes followed by stereoselective reduction of the Reformatsky adduct. The absolute configuration of the products was determined by comparison with literature data and by 1H NMR NOESY experiments. The observed stereoselectivities can be explained in terms of a boat transition state. Functionalization of the aldehyde and removal or transformation of the chiral sulfoxide will allow this methodology to be applied to the total synthesis of biologically active molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Diastereoselective Synthesis of New P‐Stereogenic (ortho‐Hydroxyaryl)diazaphospholidine–Borane Complexes by a Totally Stereoselective P–O to P–C Migration Rearrangement
Authors: Ngono Christian J. , Constantieux Thierry , Buono Gérard 
Published: December 2005

AbstractThe totally diastereoselective synthesis of new P‐stereogenic (o‐hydroxyaryl)diazaphospholidines, in the form of their borane complexes 4a–4h, is described. The efficiency of this procedure is based both, on a one‐pot and totally diastereoselective synthesis of the precursors (ortho‐bromoaryloxy)diazaphosphospholidine–borane complexes 3a–3h, and on a stereoselective P–O to P–C migration rearrangement. A X‐ray diffraction study of the structures of the product 4f and his precursor 3f shows unambiguously the totally stereoselectivity of the P–O to P–C rearrangement with clean retention of the phosphorus configuration.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Effective Debye length in closed nanoscopic systems: A competition between two length scales
Authors: Tessier Frédéric , Slater Gary W. 
Published: December 2005

AbstractThe Poisson‐Boltzmann equation (PBE) is widely employed in fields where the thermal motion of free ions is relevant, in particular in situations involving electrolytes in the vicinity of charged surfaces. The applications of this non‐linear differential equation usually concern open systems (in osmotic equilibrium with an electrolyte reservoir, a semi‐grand canonical ensemble), while solutions for closed systems (where the number of ions is fixed, a canonical ensemble) are either not appropriately distinguished from the former or are dismissed as a numerical calculation exercise. We consider herein the PBE for a confined, symmetric, univalent electrolyte and quantify how, in addition to the Debye length, its solution also depends on a second length scale, which embodies the contribution of ions by the surface (which may be significant in high surface‐to‐volume ratio micro‐ or nanofluidic capillaries). We thus establish that there are four distinct regimes for such systems, corresponding to the limits of the two parameters. We also show how the PBE in this case can be formulated in a familiar way by simply replacing the traditional Debye length by an effective Debye length, the value of which is obtained numerically from conservation conditions. But we also show that a simple expression for the value of the effective Debye length, obtained within a crude approximation, remains accurate even as the system size is reduced to nanoscopic dimensions, and well beyond the validity range typically associated with the solution of the PBE.
Continuous separation of microparticles by size with Direct current‐dielectrophoresis
Authors: Kang Kwan Hyoung , Kang Yuejun , Xuan Xiangchun , Li Dongqing 
Published: December 2005

AbstractDirect current‐dielectrophoresis (DC‐DEP), the induced motion of the dielectric particles in a spatially nonuniform DC electric field, is demonstrated to be a highly efficient method to separate the microparticles by size. The locally nonuniform electric field is generated by an insulating block fabricated inside a polydimethylsiloxane microchannel. The particle experiences a negative DEP (accordingly a repulsive force) at the corners of the block, where the local electric‐field strength is the strongest. Thus, the particle deviates from the streamline and the degree of deviation is dependent on the DEP force (i.e., the particle size). Combined with the electrokinetic flow, mixed polystyrene particles of a few micrometers difference in diameter can be continuously separated into distinct reservoirs. For separating target particles of a specific size, it is required to simply adjust the voltage outputs of the electrodes. A numerical model based on the Lagrangian tracking method is developed to simulate the particle motion and the results showed a reasonable agreement with the experimental data.
Electrophoresis of soft particles: Analytic approximations
Authors: Ohshima Hiroyuki 
Published: December 2005

AbstractAn approximate analytic expression is derived for the electrophoretic mobility of a weakly charged spherical soft particle (i.e., a hard particle covered with a weakly charged polyelectrolyte layer) on the basis of the general mobility expression for soft particles (Ohshima, H., J. Colloid Interface Sci. 2000, 228, 190–193). The obtained mobility expression, which reproduces various approximate results so far derived and gives some new mobility formulas, covers all types of weakly charged soft particles with arbitrary values of the thickness of polymer layer, the radius of the particle core, the electrophoretic softness, and the Debye length, including spherical polyelectrolytes with no particle core as well as spherical hard particles with no polyelectrolyte layer.
A new type of migrating zone boundary in electrophoresis: 2. Transient sample zone shapes
Authors: Gebauer Petr , Malá Zdena , Boček Petr 
Published: December 2005

AbstractA new type of migrating zone boundary in electrophoresis is presented theoretically and evidenced experimentally. This type of the boundary (called hybrid boundary) shows simultaneously a steady‐state part with self‐sharpening properties and an unsteady‐state part with time‐dependent electromigration dispersion. It is shown that a sample zone may possess a hybrid boundary both as its front and rear one simultaneously. In such a case, the evolution of a sample zone injected originally as a rectangular pulse exhibits very complex transient shapes before it reaches the well‐known fronting or tailing triangular shape. Depending on the stage at which detection of such a sample zone occurs, variable and peculiar‐shape peaks may appear in the electropherogram. Based on theoretical predictions, experimental examples of the above‐mentioned phenomena are presented in this contribution for direct and indirect UV absorbance detection of sample zones. Excellent agreement of theoretical predictions with the experiments has been found. The knowledge of hybrid boundaries is of key significance for correct interpretation of records of CE analyses in practice.