bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ipsilateral breast tumor recurrence (IBTR) after breast‐conserving treatment for early breast cancer
Authors: Komoike Yoshifumi , Akiyama Futoshi , Iino Yuichi , Ikeda Tadashi , Akashi‐Tanaka Sadako , Ohsumi Shozo , Kusama Mikihiro , Sano Muneaki , Shin Eisei , Suemasu Kimito , Sonoo Hiroshi , Taguchi Tetsuya , Nishi Tsunehiro , Nishimura Reiki , Haga Shunsuke , Mise Keiichi , Kinoshita Takayuki , Murakami Shigeru , Yoshimoto Masataka , Tsukuma Hideaki , Inaji Hideo 
Published: December 2005

AbstractBACKGROUNDThe clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long‐term follow‐up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group.METHODSPatients (N = 1901)with unilateral breast cancer ≤ 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan–Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR.RESULTSAt a median follow‐up time of 107 months, the 10‐year overall and disease‐free survival rates were 83.9% and 77.8%, respectively. The 10‐year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10‐year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676–5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis.CONCLUSIONSYoung age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases. Cancer 2006. © 2005 American Cancer Society.
Use of the National Cancer Data Base to develop clinical trials accrual targets that are appropriate for minority ethnicity patients
Authors: Newman Lisa A. , Lee Cheryl T. , Parekh Lina Patel , Stewart Andrew K. , Thomas Charles R. , Beltran Robert A. , Lucci Anthony , Green Bettye , Ota David , Nelson Heidi 
Published: December 2005

AbstractBACKGROUNDDisparities in cancer outcome among different subsets of the American population related to ethnic background have been well documented. Clinical trials represent the most powerful strategy for improving cancer treatments, but racial and ethnic minority patients are frequently underrepresented among patients accrued to these protocols. Proof of comparable efficacy for a promising cancer therapy in different groups of patients requires diversity in the clinical trial populations so that study results will be generalizable. Appropriate targets for accrual of minority ethnicity patients have not previously been defined.METHODSThe National Cancer Database (NCDB) is maintained jointly by the American Cancer Society and the American College of Surgeons. Information submitted by tumor registries throughout the United States represents an estimated 70% of newly diagnosed cancer cases. The authors analyzed NCDB reports on ethnic distribution of patients with breast, prostate, nonsmall cell lung, and colorectal cancer, stratified by stage of disease at diagnosis.RESULTSAfrican Americans with cancer of the breast and prostate had the most notable patterns of disproportionate representation among populations with advanced‐stage disease. The authors compiled a table of suggested accrual targets for selected solid‐organ cancers based on NCDB stage‐specific reports.CONCLUSIONSClinical trial results will be more meaningful if participating patients reflect the site‐ and stage‐specific populations that are under study. The authors recommended that clinical trial investigators incorporate accrual targets for minority ethnicity populations into the study design. Cancer 2006. © 2005 American Cancer Society.
Characterization of human fetal osteoblasts by microarray analysis following stimulation with 58S bioactive gel‐glass ionic dissolution products
Authors: Christodoulou Ioannis , Buttery Lee D. K. , Tai Guangping , Hench Larry L. , Polak Julia M. 
Published: December 2005

AbstractBioactive glasses dissolve upon immersion in culture medium, releasing their constitutive ions in solution. There is evidence suggesting that these ionic dissolution products influence osteoblast‐specific processes. Here, we investigated the effect of 58S sol–gel‐derived bioactive glass (60 mol % SiO2, 36 mol % CaO, 4 mol % P2O5) dissolution products on primary osteoblasts derived from human fetal long bone explant cultures (hFOBs). We used U133A human genome GeneChip® oligonucleotide arrays to examine 22,283 transcripts and variants, which represent over 18,000 well‐substantiated human genes. Hybridization of samples (biotinylated cRNA) derived from monolayer cultures of hFOBs on the arrays revealed that 10,571 transcripts were expressed by these cells, with high confidence. These included transcripts representing osteoblast‐related genes coding for growth factors and their associated molecules or receptors, protein components of the extracellular matrix (ECM), enzymes involved in degradation of the ECM, transcription factors, and other important osteoblast‐associated markers. A 24‐h treatment with a single dosage of ionic products of sol–gel 58S dissolution induced the differential expression of a number of genes, including IL‐6 signal transducer/gp130, ISGF‐3/STAT1, HIF‐1 responsive RTP801, ERK1 p44 MAPK (MAPK3), MAPKAPK2, IGF‐I and IGFBP‐5. The over 2‐fold up‐regulation of gp130 and MAPK3 and down‐regulation of IGF‐I were confirmed by real‐time RT‐PCR analysis. These data suggest that 58S ionic dissolution products possibly mediate the bioactive effect of 58S through components of the IGF system and MAPK signaling pathways. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Porous akermanite scaffolds for bone tissue engineering: Preparation, characterization, and in vitro studies
Authors: Wu Chengtie , Chang Jiang , Zhai Wanyin , Ni Siyu , Wang Junying 
Published: December 2005

AbstractThe aim of this study was to develop a bioactive, degradable, and cytocompatible akermanite (Ca2MgSi2O7) scaffold with high porosity and pore interconnectivity. In brief, porous akermanite scaffolds were prepared using polymer sponge method. The porosity and corresponding compressive strength were evaluated. The in vitro degradability was investigated by soaking the scaffolds in Ringer's solution. Hydroxyapatite (HAp)‐formation ability of akermantite scaffolds in simulated body fluid (SBF) and the effect of ionic products from the scaffolds dissolution on osteoblasts were investigated. In addition, bone marrow stromal cells (BMSC) adhesion and proliferation on the scaffolds were evaluated. Differentiation of the cells was assessed by measuring alkaline phosphatase (ALP) activity. The results showed that akermanite scaffolds possessed 63.5–90.3% of porosity, with a corresponding compressive strength between 1130 and 530 kPa. The weight loss of the scaffolds and ionic content of the Ringer's solution increased with the increase in soaking time, indicating the degradability of scaffolds. HAp was formed on the scaffolds in SBF and the ionic products from akermanite scaffolds dissolution stimulated osteoblasts proliferation, indicating good in vitro bioactivity. Furthermore, BMSC adhered and spread well on akermanite scaffolds and proliferated with the increase in the culture time, and the differentiation rate of osteoblasts on scaffolds was comparable to that on blank culture plate control. Our results suggested that akermanite scaffolds were bioactive, degradable, and cytocompatible, and might be used as bone tissue 1engineering materials. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Cardiac glycoside inhibits IL‐8‐induced biological responses by downregulating IL‐8 receptors through altering membrane fluidity
Authors: Manna Sunil K. , Sreenivasan Yashin , Sarkar Abira 
Published: December 2005

AbstractConsidering the potential role of interleukin‐8 (IL‐8) in inflammation, angiogenesis, tumorogenesis, and metastasis, and the involvement of different cell types especially neutrophils and macrophages in those processes, the regulation of IL‐8‐mediated biological responses is important. In this report we provide evidences that oleandrin, a cardiac glycoside potentially inhibited IL‐8‐, formyl peptide (FMLP)‐, EGF‐, or nerve growth factor (NGF)‐, but not IL‐1‐ or TNF‐induced NF‐κB activation in macrophages. Oleandrin inhibited IL‐8‐, but not TNF‐induced NF‐κB‐dependent genes expression. Oleandrin inhibited the binding of IL‐8, EGF, or NGF, but not IL‐1 or TNF. It decreased almost 79% IL‐8 binding without altering affinity towards IL‐8 receptors and this inhibition of IL‐8 binding was observed in isolated membrane. The IL‐8, anti‐IL‐8Rs antibodies, or protease inhibitors were unable to protect oleandrin‐mediated inhibition of IL‐8 binding. Phospholipids significantly protected oleandrin‐mediated inhibition of IL‐8 binding thereby restoring IL‐8‐induced NF‐κB activation. Oleandrin altered the membrane fluidity as detected by microviscosity parameter and a decrease in diphenylhexatriene, a lipid binding fluorophore binding in a dose‐dependent manner. Overall, our results suggest that oleandrin inhibits IL‐8‐mediated biological responses in diverse cell types by modulating IL‐8Rs through altering membrane fluidity and microviscosity. The study might help to regulate IL‐8‐mediated biological responses involved in inflammation, metastasis, and neovascularization. J. Cell. Physiol. 207: 195–207, 2006. © 2005 Wiley‐Liss, Inc.
Requirement of an IκB‐β COOH terminal region protein for acidic‐adaptation in CHO cells
Authors: Lao Qizong , Fukamachi Toshihiko , Saito Hiromi , Kuge Osamu , Nishijima Masahiro , Kobayashi Hiroshi 
Published: December 2005

AbstractWe previously reported that an IκB‐β COOH terminal region protein (designated CTIB) was essential for the proliferation of CHO cells under acidic stress (Lao et al., . J Cell Physiol 203(1):186–192). In order to investigate the mechanisms underlying the requirement of CTIB for acidic adaptation, CTIB was silenced with an RNAi technique in CHO cells. CTIB silencing resulted in those cells completely failing to proliferate and maintain intracellular pH (pHi) homeostasis at an extracellular pH (pHe) of 6.3. An increased activation of p38 MAP kinase was induced by CTIB silencing at the low pH value. CTIB was only present in the cytoplasm and co‐immunoprecipitation of the cytoplasmic fraction revealed that the loss of CTIB led to a loss of p65 in the immunoprecipitate complex. CTIB silencing reduced both the decrease in p65 and the increase in p50 in the nucleus when the cells were incubated at pHe 6.3. In cells with CTIB silenced, the transcriptions of p65, p105, and IL1‐β were suppressed, and decreases in both the transcription and activity of MnSOD were observed at pHe 6.3. Suppression of these genes suggested a suppressed NF‐κB activity since p105, IL1‐β, and MnSOD were target genes of NF‐κB. Our data demonstrated that CTIB functioned to prevent the over‐accumulation of p65 in the nucleus, ensuring the appropriate composition of the NF‐κB complex in the nucleus to respond to stimuli under acidic conditions. J. Cell. Physiol. 207: 238–243, 2006. © 2005 Wiley‐Liss, Inc.
Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells
Authors: Han Chang , Michalopoulos George K. , Wu Tong 
Published: December 2005

AbstractRecent evidence indicates that cyclooxygenase‐2 (COX‐2) and epidermal growth factor receptor (EGFR) are involved in hepatocarcinogenesis. This study was designed to evaluate the possible interaction between the COX‐2 and EGFR signaling pathways in human hepatocellular carcinoma (HCC) cells. Immunohistochemical analysis using serial sections of human HCC tissues revealed positive correlation between COX‐2 and EGFR in HCC cells (P < 0.01). Overexpression of COX‐2 in cultured HCC cells (Hep3B) or treatment with PGE2 or the selective EP1 receptor agonist, ONO‐DI‐004, increased EGFR phosphorylation and tumor cell invasion. The PGE2‐induced EGFR phosphorylation and cell invasiveness were blocked by the EP1 receptor siRNA or antagonist ONO‐8711 and by two EGFR tyrosine kinase inhibitors, AG1478 and PD153035. The EP1‐induced EGFR transactivation and cell invasion involves c‐Src, in light of the presence of native binding complex of EP1/Src/EGFR and the inhibition of PGE2‐induced EGFR phosphorylation and cell invasion by the Src siRNA and the Src inhibitor, PP2. Further, overexpression of COX‐2 or treatment with PGE2 also induced phosphorylation of c‐Met, another receptor tyrosine kinase critical for HCC cell invasion. Moreover, activation of EGFR by EGF increased COX‐2 promoter activity and protein expression in Hep3B and Huh‐7 cells, whereas blocking PGE2 synthesis or EP1 attenuated EGFR phosphorylation induced by EGF, suggesting that the COX‐2/PGE2/EP1 pathway also modulate the activation of EGFR by its cognate ligand. These findings disclose a cross‐talk between the COX‐2/PGE2/EP1 and EGFR/c‐Met signaling pathways that coordinately regulate human HCC cell invasion. J. Cell. Physiol. 207: 261–270, 2006. © 2005 Wiley‐Liss, Inc.
Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes
Authors: Zinman T. , Shneyvays V. , Tribulova N. , Manoach M. , Shainberg A. 
Published: December 2005

AbstractIn this study, we examined the acute effects of thyroid hormones (TH) T3 and T4, leading to improvement of myocardial function through activation of Ca2+ extrusion mechanisms and, consequently, prevention of intracellular calcium overload. Extracellular calcium elevation from 1.8 to 3.8 mM caused immediate increase in intracellular calcium level ([Ca2+]i) in newborn cardiomyocyte cultures. Administration of 10 or 100 nM T3 or T4 rapidly (within 10 sec) decreased [Ca2+]i to its control level. Similar results were obtained when [Ca2+]i was elevated by decreasing extracellular Na+ concentration, causing backward influx of Ca2+ through Na+/Ca2+ exchanger, or by administration of caffeine, releasing Ca2+ from the sarcoplasmic reticulum (SR). Under these conditions, T3 or T4 decreased [Ca2+]i. T3 and T4 also exhibited protective effects during ischemia. T3 or T4 presence during hypoxia for 120 min in culture medium restricted the increase of [Ca2+]i and prevented the pathological effects of its overload. An inhibitor of SR Ca2+‐ATPase (SERCA2a), thapsigargin, increases [Ca2+]i and in its presence neither T3 nor T4 had any effect on the [Ca2+]i level. The reduction of [Ca2+]i level by T3 and T4 was also blocked in the presence of H‐89 (a PKA inhibitor), and by calmodulin inhibitors. The effect of TH on the reduction of [Ca2+]i was prevented by propranolol, indicating that the hormones exert their effect through interaction with adrenergic receptors. These results support our hypothesis that TH prevent calcium overload in newborn rat cardiomyocytes, most likely by a direct, acute, and nongenomic effect on Ca2+ transport into the SR. J. Cell. Physiol. 207: 220–231, 2006. © 2005 Wiley‐Liss, Inc.
Oncogenic met receptor induces cell‐cycle progression in Xenopus oocytes independent of direct Grb2 and Shc binding or mos synthesis, but requires phosphatidylinositol 3‐kinase and raf signaling
Authors: Mood Kathleen , Saucier Caroline , Ishimura Akihiko , Bong Yong‐Sik , Lee Hyun‐Shik , Park Morag , Daar Ira O. 
Published: December 2005

AbstractBiological responses of hepatocyte growth factor (HGF) are mediated by the Met receptor tyrosine kinase. Although HGF is a potent mitogen for a variety of cells, the signals required for cell‐cycle progression by the Met/HGF receptor are poorly defined. In this study, we have used the Xenopus oocyte system to define the role of various Met proximal‐binding partners and downstream signaling pathways in cell‐cycle regulation. We show that cell‐cycle progression and activation of MAPK and JNK mediated by the oncogenic Met receptor, Tpr‐Met, are dependent on its kinase activity and the presence of the twin phosphotyrosine (Y482 & Y489) residues in its C‐terminus, but that the recruitment of Grb2 and Shc adaptor proteins is dispensable, implicating other signaling molecules. However, using Met receptor oncoproteins engineered to recruit specific signaling proteins, we demonstrate that recruitment of Grb2 or Shc adaptor proteins is sufficient to induce cell‐cycle progression and activation of MAPK and JNK, while the binding of phospholipase‐Cγ or phosphatidylinositol 3‐kinase alone fails to elicit these responses. Using various means to block phosphatidylinositol 3‐kinase, phospholipase‐Cγ, MEK, JNK, Mos, and Raf1 activity, we show that unlike the fibroblast growth factor receptor, MEK‐dependent and independent signaling contribute to Met receptor‐mediated cell‐cycle progression, but phospholipase‐Cγ or JNK activity and Mos synthesis are not critical. Notably, we demonstrate that Raf1 and phosphatidylinositol 3‐kinase signaling are required for cell‐cycle progression initiated by the Met receptor, a protein frequently deregulated in human tumors. J. Cell. Physiol. 207: 271–285, 2006. © 2005 Wiley‐Liss, Inc.
Pkn Is a novel partner of cyclin T2a in muscle differentiation
Authors: Cottone Giuliano , Baldi Alfonso , Palescandolo Emanuele , Manente Lucrezia , Penta Roberta , Paggi Marco G. , De Luca Antonio 
Published: December 2005

AbstractWith the aim to find novel partners of human Cyclin T2a, we performed a two‐hybrid screening in yeast using the full‐length cDNA of this cyclin as bait, and a human heart cDNA library as preys source. Upon several interesting genes selected, our attention has been focused on the cDNA coding for PKNα, a fatty acid‐ and Rho‐activated serine/threonine protein kinase, having a catalytic domain homologous to protein kinase C family. Co‐immunoprecipitation and in vitro pull‐down assays independently confirmed the interaction between the two proteins. Luciferase assays, performed on NIH3T3 cell extracts after transfection with a MyoD‐responsive promoter, pointed out that PKNα was able to enhance MyoD‐dependent transcription, and that this effect was further increased when cyclin T2a was co‐overexpressed. Finally, overexpression of both Cyclin T2a and PKNα in C2C12 cells strongly enhanced the expression of myogenic differentiation markers, such as Myogenin and Myosin Heavy Chain, during starvation‐induced differentiation. Taken together, our data strengthen the hypothesis that Cyclin T2a plays a role in muscle differentiation, and propose PKNα as a novel partner of Cyclin T2a in this process. J. Cell. Physiol. 207: 232–237, 2006. © 2005 Wiley‐Liss, Inc.
CYR61 (CCN1) Protein Expression during Fracture Healing in an Ovine Tibial Model and Its Relation to the Mechanical Fixation Stability
Authors: Lienau Jasmin , Schell Hanna , Epari Devakara R. , Schütze Norbert , Jakob Franz , Duda Georg N. , Bail Hermann J. 
Published: December 2005

AbstractThe formation of new blood vessels is a prerequisite for bone healing. CYR61 (CCN1), an extracellular matrix‐associated signaling protein, is a potent stimulator of angiogenesis and mesenchymal stem cell expansion and differentiation. A recent study showed that CYR61 is expressed during fracture healing and suggested that CYR61 plays a significant role in cartilage and bone formation. The hypothesis of the present study was that decreased fixation stability, which leads to a delay in healing, would lead to reduced CYR61 protein expression in fracture callus. The aim of the study was to quantitatively analyze CYR61 protein expression, vascularization, and tissue differentiation in the osteotomy gap and relate to the mechanical fixation stability during the course of healing. A mid‐shaft osteotomy of the tibia was performed in two groups of sheep and stabilized with either a rigid or semirigid external fixator, each allowing different amounts of interfragmentary movement. The sheep were sacrificed at 2, 3, 6, and 9 weeks postoperatively. The tibiae were tested biomechanically and histological sections from the callus were analyzed immunohistochemically with regard to CYR61 protein expression and vascularization. Expression of CYR61 protein was upregulated at the early phase of fracture healing (2 weeks), decreasing over the healing time. Decreased fixation stability was associated with a reduced upregulation of the CYR61 protein expression and a reduced vascularization at 2 weeks leading to a slower healing. The maximum cartilage callus fraction in both groups was reached at 3 weeks. However, the semirigid fixator group showed a significantly lower CYR61 immunoreactivity in cartilage than the rigid fixator group at this time point. The fraction of cartilage in the semirigid fixator group was not replaced by bone as quickly as in the rigid fixator group leading to an inferior histological and mechanical callus quality at 6 weeks and therefore to a slower healing. The results supply further evidence that CYR61 may serve as an important regulator of bone healing. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Disseminated toxoplasmosis resulting in graft failure in a cord blood stem cell transplant recipient
Authors: Goebel W. Scott , Conway James H. , Faught Philip , Vakili Saeed T. , Haut Paul R. 
Published: December 2005

AbstractToxoplasmosis is an infrequent infection with a high mortality rate in hematopoietic stem cell transplant recipients, and is usually caused by reactivation of prior, latent infection upon intensive immunosuppression. We report a case of fatal disseminated toxoplasmosis, diagnosed at autopsy, in a 7‐year‐old boy who received a cord blood graft for recurrent acute lymphoblastic leukemia. This case represents both the first reported case of toxoplasmosis in an engrafted cord blood recipient, and also of graft failure due to toxoplasmosis. Recommendations for toxoplasmosis diagnosis, treatment, and prophylaxis in stem cell transplant recipients are reviewed. Pediatr Blood Cancer 2007;48:222–226. © 2006 Wiley‐Liss, Inc.