bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor‐positive breast cancer
Authors: Cataliotti Luigi , Buzdar Aman U. , Noguchi Shinzaburo , Bines Jose , Takatsuka Yuichi , Petrakova Katarina , Dube Pierre , Tosello de Oliveira Celia 
Published: April 2006

AbstractBACKGROUNDThe Pre‐Operative “Arimidex” Compared to Tamoxifen (PROACT) study was a randomized, multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large, operable (T2/3, N0‐2, M0), or potentially operable (T4b, N0‐2, M0) breast cancer. The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated.METHODSPatients with hormone receptor‐positive breast cancer received anastrozole (n = 228) or tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary surgery.RESULTSObjective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0% and 46.2% of patients, respectively (caliper measurements). In hormonal therapy‐only patients (n = 314), feasible surgery at baseline improved after 3 months in 43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04). In the intent‐to‐treat population, improvement in feasible surgery at baseline to actual surgery at 3 months was found to be numerically higher in the anastrozole group compared with the tamoxifen group, although this difference did not reach significance. Drug‐related adverse events were reported in 20.2% and 18.1% of patients, respectively, in the anastrozole and tamoxifen groups.CONCLUSIONSAnastrozole is an effective and well‐tolerated preoperative therapy, producing clinically beneficial tumor downstaging and reductions in tumor volume. These effects enable more minimal surgical interventions in patients scheduled for mastectomy, and mastectomy in patients with previously inoperable tumors. Anastrozole appears to be at least as effective as tamoxifen in this setting, and more effective than tamoxifen in certain clinically relevant subgroups. Cancer 2006. © 2006 American Cancer Society.
Phase II trial of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer
Authors: Hoff Paulo M. , Wolff Robert A. , Xiong Henry , Jones Dennie , Lin Edward , Eng Cathy , Dutta Ankhi , Bogaard Karla R. , Abbruzzese James L. 
Published: April 2006

AbstractBACKGROUNDBoth irinotecan and oxaliplatin are active agents in the treatment of patients with metastatic colorectal cancer, and there is a strong preclinical rationale for combining these 2 agents. Therefore, a Phase II trial was designed and conducted to determine the efficacy and tolerability of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer.METHODSPatients with previously untreated metastatic colorectal cancer received irinotecan at a dose of 175 mg/m2 and oxaliplatin at a dose of 130 mg/m2, both given intravenously every 3 weeks. Objective responses were evaluated every 2 courses and were confirmed at least 4 weeks after the initial determination.RESULTSFifty‐five patients were enrolled and treated in the current trial. Of the 53 patients whose responses were evaluable, 18 (34%) achieved a partial response, 27 (51%) had stable disease, and 8 (15%) developed disease progression as their best response to the treatment. The intent‐to‐treat median survival for all patients was 16.4 months and the time to progression was 4.8 months. All 55 patients were available for toxicity analysis (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria). The most common Grade 3‐4 toxic effect was neutropenia, which was reported to occur in 22 patients (40%).CONCLUSIONSThe combination of irinotecan and oxaliplatin appears to be safe and active when used to treat patients with metastatic colorectal cancer. Treatment results with this regimen were similar to those reported for other combined frontline chemotherapy regimens for colorectal cancer. When this particular regimen wa used, neutropenia was found to be the predominant toxicity. Cancer 2006. © 2006 American Cancer Society.
Molecular genetic cascades for external genitalia formation: An emerging organogenesis program
Authors: Yamada G. , Suzuki K. , Haraguchi R. , Miyagawa S. , Satoh Y. , Kamimura M. , Nakagata N. , Kataoka H. , Kuroiwa A. , Chen Y. 
Published: April 2006

AbstractExternal genitalia are anatomical structures located at the posterior embryonic region as part of several urogenital/reproductive organs. The embryonic anlage of the external genitalia, the genital tubercle (GT) develops as a bud‐shaped structure with an initial urethral plate and later urethra. Embryonic external genitalia are considered to be one of the appendages. Recent experiments suggest that essential regulatory genes possess similar functions for the outgrowth regulation of the GT and limb appendages. The transient embryonic epithelia located in the distal GT are called the distal urethral epithelium (DUE) regulating, at least in part, the (distal) GT development. This review covers the available data about early patterning of GT and discusses the molecular developmental similarities and points of divergence between the different appendages. Development of the male and female external genitalia is also reviewed. Developmental Dynamics 235:1738–1752, 2006. © 2006 Wiley‐Liss, Inc.
No evidence for dualism in function and receptors: PD‐L2/B7‐DC is an inhibitory regulator of human T cell activation
Authors: Pfistershammer Katharina , Klauser Christoph , Pickl Winfried F. , Stöckl Johannes , Leitner Judith , Zlabinger Gerhard , Majdic Otto , Steinberger Peter 
Published: April 2006

AbstractThe B7 family member programmed‐death‐1‐ligand 2 (PD‐L2/B7‐DC) is a ligand for programmed‐death‐receptor 1 (PD‐1), a receptor involved in negative regulation of T cell activation. Several independent studies have reported that PD‐L2, however, can also potently costimulate murine T cells via an additional yet unidentified receptor. In this study, we evaluated the contribution of PD‐L2 to the activation of human T cells using a novel system of engineered T cell stimulators that expresses membrane‐bound anti‐CD3 antibodies. Analyzing early activation markers, cytokine production and proliferation, we found PD‐L2 to consistently inhibit T cell activation. PD‐L2 inhibition affected CD4+ and CD8+ T cells and was not abrogated by costimulation via CD28. Blocking PD‐1 reverted the inhibitory effect of PD‐L2, demonstrating involvement of this pathway. In human T cells, we found no evidence for any of the costimulatory effects described for PD‐L2 in murine systems. In line with our functional data that do not point to stimulatory PD‐L2‐ligands, we show that binding of PD‐L2‐immunoglobulin to activated human T cells is abrogated by PD‐1 antibodies. Our results demonstrate that PD‐L2 negatively regulates human T cell activation and thus might be a candidate molecule for immunotherapeutic approaches aimed to attenuate pathological immune responses.
Priming of CD8+ T cell responses following immunization with heat‐killed Plasmodium sporozoites
Authors: Hafalla Julius C. R. , Rai Urvashi , Morrot Alexandre , Bernal‐Rubio Dabeiba , Zavala Fidel , Rodriguez Ana 
Published: April 2006

AbstractProtective immune responses against malaria are induced by immunization with radiation‐attenuated Plasmodium sporozoites. In contrast, non‐viable, heat‐killed sporozoites do not induce protection, emphasizing the requirement for live parasites to achieve effective immune responses. Using an experimental system with CD8+ T cells from T cell receptor‐transgenic mice, we analyzed the primary CD8+ T cell responses elicited by heat‐killed inactivated sporozoites. We found that the numbers of specific CD8+ T cells induced were much lower compared to when immunizing with attenuated sporozoites; however, the kinetics of activation and the phenotype of these T cells were similar in both groups. Despite their low frequency after priming, high numbers of specific CD8+ T cells were observed after boosting with a recombinant vaccinia virus. Upon induction of the recall response, the same level of protection was observed when either heat‐killed or attenuated sporozoites were used for priming. We propose that live parasites are not critical for the induction of memory T cell populations against the malaria liver stages.
Grass ley set‐aside and soil organic matter dynamics on sandy soils in Shropshire, UK
Authors: Fullen Michael A. , Booth Colin A. 
Published: April 2006

AbstractErosion plot studies at the Hilton Experimental Site, Shropshire, UK, evaluated the effects of set‐aside on runoff, erosion and soil organic matter (SOM) dynamics. Ten runoff plots (slope angles 7–15°) were put to a grass ley in April 1991. Runoff and erosion rates during nine years were low, despite the occurrence of potentially erosive rains. Mean runoff was 0·24 per cent of precipitation (SD = 0·20, n = 89 plot years), compared with a 15‐year mean value of 0·13 per cent (SD = 0·04) on permanent (control) grassland. The mean plot erosion rate was 0·21 t ha−1 a−1 (SD = 0·14, n = 69 plot years). Mean SOM content increased consistently and sign fi a tly on the set‐aside plots, by a mean value of 1·07 per cent by weight (i.e. 1·07 g per 100 g of soil) in ten ye rs, from 2·04 per cent (1991) to 3·11 per cent (2001). Soil erodibility after six years of set‐aside (sampling date 24 April 1997) was determined using a drip‐screen rainfall simulator. Soil aggregate stability was higher on the grassed soils, compared with set‐aside and bare arable soils. Despite no significant (P > 0·05) differences be w en grassland and set‐asid oils, both these treatments were s gnificantly (P < 0·001) diff rent from bare soils. Contrary to the usually strong relationship between SOM and clay content, the percentage silt (r = 0·52, P < 0·001, n = 50) exhibited a stronger correlation with SOM than percentage clay content (r = 0·37, P < 0·01, n = 50). Furthermore, there were equally strong correlations between SOM and cumulative particle size fractions of both clay and silt contents (r = 0·51, P < 0·001, n = 50). In the absence of significant quantities of clay in these sandy soils, silts assist binding of SOM, which has significance for assessing soil carbon sequestration potential. Finally, future SOM and soil organic carbon benchmark work at the Hilton Site will improve harmonization of global SOM databases and enhance international estimates of rates and potential for soil carbon sequestration. Copyright © 2006 John Wiley & Sons, Ltd.
Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan
Authors: Yang San Nan , Liu Chieh‐An , Chung Mei‐Yung , Huang Hsin‐Chun , Yeh Geng‐Chang , Wong Chih‐Shung , Lin Wei‐Wen , Yang Chun‐Hua , Tao Pao‐Luh 
Published: April 2006

AbstractInfants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD‐95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD‐95 expression at P14 followed by an age‐dependent improvement. In addition, prenatal morphine exposure reduced not only the expression ofnNOS and the phosphorylation of cAMP responsive element‐binding protein at serine 133 (CREBSerine‐133), but also the magnitude of long‐term depression (LTD) at P14. Subsequently, the morphine‐treated offspring exhibited impaired performance in long‐term learning and memory at later ages (P28–29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD‐95,nNOS, the phosphorylation of CREBSerine‐133, and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long‐term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine‐addicted mother and provide tentative therapeutic strategy. © 2006 Wiley‐Liss, Inc.
Skewed expression of natural‐killer (NK)‐associated antigens on lymphoproliferations of large granular lymphocytes (LGL)
Authors: Fischer Lars , Hummel Michael , Burmeister Thomas , Schwartz Stefan , Thiel Eckhard 
Published: April 2006

AbstractKiller‐immunoglobulin‐like receptors (KIR) or C‐type lectin‐like receptors are heterogeneously expressed on NK cells and small subsets of T cells and might provide a new diagnostic tool for LGL lymphoproliferations (LGLL). We investigated the diagnostic impact of these cell surface molecules in T‐ and NK‐type LGLL. Using three‐color flow cytometry we examined the expression patterns of KIR (CD158a/b/e/i), CD85j, lectin‐like receptors (CD94, CD161, NKG2A/D) and natural cytotoxicity receptors (NKp30/44/46) in 13 patients with LGLL (10 T‐, 3 NK‐LGLL) and compared them to those of the corresponding lymphocyte subsets in 20 control subjects. The presence of clonal TCR‐gamma rearrangements and of Epstein Barr virus‐ (EBV) DNA were evaluated by PCR.All patients exhibited an altered expression of NK‐associated markers. KIR were either lacking (6/13) or overexpressed (7/13). CD94 expression was significantly higher in all LGLL. NKG2A expression was significantly higher in NK‐LGLL. Absence or overexpression was observed for NKG2A in T‐LGLL and CD161 in most T/NK‐LGLL. In NK‐LGLL expression of NKp30 and NKp46 was significantly decreased, whereas CD85j was overexpressed.We consistently found a skewed expression pattern of novel NK markers as a pathological feature of LGLL. These antigens should be included in the diagnostic workup of this rare disease. Copyright © 2006 John Wiley & Sons, Ltd.
Bacteria and cell cytocompatibility studies on coated medical grade titanium surfaces
Authors: Harris L. G. , Mead L. , Müller‐Oberländer E. , Richards R. G. 
Published: April 2006

AbstractAcute and chronic osteomyelitis caused by staphylococci can be difficult to treat by conventional means and often has marked consequences for the patient. Current methods of treatment involve the use of systemic antibiotics, the local implantation of nondegradable drug carriers, and surgical debridement. A possible solution that could prevent initial bacterial adhesion could be to modify the implant surface with an antimicrobial coating while maintaining biocompatibility to host cells. This study describes the cytocompatibility evaluation of different coatings (poly(D,L‐lactide) (PDLLA), politerefate (PTF), calcium phosphate/anodic plasma‐chemical treatment (CaP/APC), polyurethane (PU), and polyvinylpyrollidone (PVP) on titanium surfaces with and without chlorhexidine diacetate (CHA) to Staphylococcus aureus, Staphylococcus epidermidis, and hTERT human fibroblasts. Surface characterization of the coatings showed no significant variation in the roughness or hydrophobicity of the coated surfaces, except the CaP/APC surface that was porous yet the smoothest, and PVP, PVP + CHA, and CaP/APC + CHA that were more hydrophilic in nature than the others. On the surfaces without CHA, both staphylococcal strains and spread fibroblasts were observed, but on the CHA impregnated surfaces few bacteria and no intact fibroblasts were seen. Flow cytometry found fewer bacteria in the media and on the surfaces containing CHA in comparison to the surfaces without CHA. The release kinetics varied from slow (over 200 h) to burst release: PDLLA > PTF > PU > CaP/APC = PVP. This study showed that PDLLA and PTF have the best potential as coatings on implants for drug delivery, as they were cytocompatible to hTERT fibroblasts, eluted CHA effectively, and passed mechanical testing. The actual release kinetics of PDLLA and PTF are important, as the amount of CHA present should remain above the minimal inhibitory concentration value for a limited time before disappearing completely. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Covalent modification of porous implants using extracellular matrix proteins to accelerate neovascularization
Authors: Williams Stuart K. , Kleinert Leigh B. , Hagen Kris M. , Clapper David L. 
Published: April 2006

AbstractHealing associated with many polymeric biomedical implants commonly involves the formation of an avascular fibrous capsule. The lack of either formation or persistence of blood vessels in formed fibrous capsules, as well as a lack of new blood vessels within porous polymeric implants, often results in poor performance of the implant. The current study evaluated the use of extracellular matrix protein modification of a commonly used biomedical implant material, expanded polytetrafluoroethylene (ePTFE), as a mechanism to increase the neovascularization both within these porous implants and in tissue that forms in the peri‐implant area. Discs of ePTFE were covalently modified with different extracellular matrix proteins including collagen type IV, fibronectin, and laminin type I. Discs were implanted into the adipose tissue of adult rats, and following a 5‐week implant phase, histologic analysis of peri‐implant tissue angiogenesis and implant neovascularization was performed. Striking differences were observed in angiogenic and neovascularization responses to matrix‐modified ePTFE when compared with control, untreated ePTFE. Fibronectin treatment resulted in an extensive inflammatory response but, relative to the degree of inflammation, limited evidence of tissue angiogenesis or polymer neovascularization. Collagen type IV treatment groups exhibited a significant increase in angiogenesis in the peri‐implant tissue with minimal evidence of implant neovascularization. In contrast to all other implant modifications, laminin type 1‐treated ePTFE samples stimulated an extensive peri‐implant tissue angiogenic response and a coordinate neovascularization of the porous interstices of the biomaterial. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Growth behavior of rat bone marrow cells on RF magnetron sputtered hydroxyapatite and dicalcium pyrophosphate coatings
Authors: Yan Yonggang , Wolke J.G.C. , De Ruijter A. , Yubao Li , Jansen J.A. 
Published: April 2006

AbstractThe aim of this study was to evaluate the osteogenic properties of magnetron sputtered dicalcium pyrophaosphate (DCPP) and hydroxylapatite (HA) coatings. Therefore, DCPP and HA coatings were deposited on grit‐blasted titanium discs. The substrates were used as‐prepared or received an additional heat treatment which changed the amorphous coating structure to a crystalline structure. Subsequently, rat bone marrow stromal cells were cultured for 1–24 days on the various substrates. DNA and alkaline phosphatase activity was determined after 1, 3, 5, 8, and 12 days of incubation. Osteocalcin expression was evaluated after 8, 12, 16, and 24 days of incubation. Scanning electron microscopical analysis of cell morphology and coating characteristics was done after 8 and 16 days of incubation. All assays were done in duplicate and in each assay all specimens were present in fourfold. Results demonstrated that the cells did not proliferate and differentiate on all amorphous coatings. SEM revealed that the amorphous coatings showed significant dissolution. On the crystalline DCPP and HA coatings an increase in DNA and alkaline phosphatase activity was seen starting at day 8 of incubation. Osteocalcin expression on the crystalline coatings started to increase at day 16 of incubation. SEM showed that the growth and differentiation of the cells was associated with extensive collagen fiber formation and surface mineralization in the form of globular accretions. Further, statistical testing revealed that proliferation and differentiation of the rat bone marrow stromal cells started significantly earlier on the crystalline HA coatings than that on the crystalline DCPP coatings. These results demonstrate that the rat bone marrow stromal cells proliferated and differentiated only on crystalline magnetron sputtered DCPP as well as HA coatings, which warrants the further in vivo analysis of the bone healing supporting properties of these coatings. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
In vivo effects of BISGMA—a component of dental composite—on male mouse reproduction and fertility
Authors: Al‐Hiyasat Ahmad S. , Darmani Homa 
Published: April 2006

AbstractThe aim of this study is to investigate the effects of the resin monomer bisphenol A glycerolate dimethacrylate (BISGMA) on adult male mouse fertility. Male Swiss mice were administered various concentrations of BISGMA (0, 25, and 100 μg/kg) for a period of 28 days, and the effects on fertility was assessed by breeding these males with untreated female mice after the exposure periods. The results showed that fertility was significantly reduced when male mice were exposed to BISGMA, in comparison with their control counterparts. In females mated with males exposed to BISGMA, there was a significant reduction in the pregnancy rates as well as the number of viable fetuses. The number of resorptions out of the total number of implantations was significantly increased in females mated with males that had been exposed to BISGMA. Furthermore, the number of females with resorptions was also significantly increased. Significant reductions in bodyweight and weights of the testis and preputial glands were also observed. The weights of the seminal vesicles were significantly increased in males exposed to BISGMA in comparison with their control counterparts. There were significant reductions in testicular sperm counts, epididymal sperm counts and in the efficiency of sperm production. In conclusion, exposure of male mice to BISGMA results in an impairment of the reproductive system and fertility. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Significantly accelerated osteoblast cell growth on aligned TiO2 nanotubes
Authors: Oh Seunghan , Daraio Chiara , Chen Li‐Han , Pisanic Thomas R. , Fiñones Rita R. , Jin Sungho 
Published: April 2006

AbstractVertically aligned yet laterally spaced nanoscale TiO2 nanotubes have been grown on Ti by anodization, and the growth of MC3T3‐E1 osteoblast cells on such nanotubes has been investigated. The adhesion/propagation of the osteoblast is substantially improved by the topography of the TiO2 nanotubes with the filopodia of growing cells actually going into the nanotube pores, producing an interlocked cell structure. The presence of the nanotube structure induced a significant acceleration in the growth rate of osteoblast cells by as much as ∼300–400%. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006