bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells
Authors: Kanazawa Ippei , Yamaguchi Toru , Yano Shozo , Yamauchi Mika , Yamamoto Masahiro , Sugimoto Toshitsugu 
Published: November 2007

Abstract

Background
Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells.

Results
Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively.

Conclusion
Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions.
TFCONES: A database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements
Authors: Lee Alison P , Yang Yuchen , Brenner Sydney , Venkatesh Byrappa 
Published: November 2007

AbstractBackgroundTranscription factors (TFs) regulate gene transcription and play pivotal roles in various biological processes such as development, cell cycle progression, cell differentiation and tumor suppression. Identifyingcis-regulatory elements associated with TF-encoding genes is a crucial step in understanding gene regulatory networks. To this end, we have used a comparative genomics approach to identify putativecis-regulatory elements associated with TF-encoding genes in vertebrates.DescriptionWe have created a database named TFCONES (TranscriptionFactor Genes & AssociatedCOnservedNoncodingElementS) (http://tfcones.fugu-sg.org) which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them. The CNEs were identified by gene-by-gene alignments of orthologous TF-encoding gene loci using MLAGAN. We also predicted putative transcription factor binding sites within the CNEs. A significant proportion of human-fugu CNEs contain experimentally defined binding sites for transcriptional activators and repressors, indicating that a majority of the CNEs may function as transcriptional regulatory elements. The TF-encoding genes that are involved in nervous system development are generally enriched for human-fugu CNEs. Users can retrieve TF-encoding genes and their associated CNEs by conducting a keyword search or by selecting a family of DNA-binding proteins.ConclusionThe conserved noncoding elements identified in TFCONES represent a catalog of highly prioritized putativecis-regulatory elements of TF-encoding genes and are candidates for functional assay.
Comparison of Genomes of Three Xanthomonas oryzae Bacteriophages
Authors: Lee Chia-Ni , Hu Rouh-Mei , Chow Teh-Yuan , Lin Juey-Wen , Chen Hui-Yi , Tseng Yi-Hsiung , Weng Shu-Fen 
Published: November 2007

Abstract

Background
Xp10 and OP1 are phages of Xanthomonas oryzae pv. oryzae (Xoo), the causative agent of bacterial leaf blight in rice plants, which were isolated in 1967 in Taiwan and in 1954 in Japan, respectively. We recently isolated the Xoo phage Xop411.

Results
The linear Xop411 genome (44,520 bp, 58 ORFs) sequenced here is 147 bp longer than that of Xp10 (60 ORFs) and 735 bp longer than that of OP1 (59 ORFs). The G+C contents of OP1 (51%) and Xop411 and Xp10 (52% each) are less than that of the host (65%). The 9-bp 3'-overhangs (5'-GGACAGTCT-3') in Xop411 and Xp10 are absent from OP1. More of the deduced Xop411 proteins share higher degrees of identity with Xp10 than with OP1 proteins, while the right end of the genomes of Xp10 and OP1, containing all predicted promoters, share stronger homology. Xop411, Xp10, and OP1 contain 8, 7, and 6 freestanding HNH endonuclease genes, respectively. These genes can be classified into five groups depending on their possession of the HNH domain (HNN or HNH type) and/or AP2 domain in intact or truncated forms. While the HNN-AP2 type endonuclease genes dispersed in the genome, the HNH type endonuclease genes, each with a unique copy, were located within the same genome context. Mass spectrometry and N-terminal sequencing showed nine Xop411 coat proteins, among which three were identified, six were assigned as coat proteins (4) and conserved phage proteins (2) in Xp10. The major coat protein, in which only the N-terminal methionine is removed, appears to exist in oligomeric forms containing 2 to 6 subunits. The three phages exhibit different patterns of domain duplication in the N-terminus of the tail fiber, which are involved in determination of the host range. Many short repeated sequences are present in and around the duplicated domains.

Conclusion
Geographical separation may have confined lateral gene transfer among the Xoo phages. The HNN-AP2 type endonucleases were more likely to transfer their genes randomly in the genome and may degenerate after successful transmission. Some repeated sequences may be involved in duplication/loss of the domains in the tail fiber genes.
Evolutionary conservation of plant gibberellin signalling pathway components
Authors: Vandenbussche Filip , Fierro Ana C , Wiedemann Gertrud , Reski Ralf , Van Der Straeten Dominique 
Published: November 2007

Abstract

Background:
Gibberellins (GA) are plant hormones that can regulate germination, elongation growth, and sex determination. They ubiquitously occur in seed plants. The discovery of gibberellin receptors, together with advances in understanding the function of key components of GA signalling in Arabidopsis and rice, reveal a fairly short GA signal transduction route. The pathway essentially consists of GID1 gibberellin receptors that interact with F-box proteins, which in turn regulate degradation of downstream DELLA proteins, suppressors of GA-controlled responses.

Results:

Arabidopsis sequences of the gibberellin signalling compounds were used to screen databases from a variety of plants, including protists, for homologues, providing indications for the degree of conservation of the pathway. The pathway as such appears completely absent in protists, the moss Physcomitrella patens shares only a limited homology with the Arabidopsis proteins, thus lacking essential characteristics of the classical GA signalling pathway, while the lycophyte Selaginella moellendorffii contains a possible ortholog for each component. The occurrence of classical GA responses can as yet not be linked with the presence of homologues of the signalling pathway. Alignments and display in neighbour joining trees of the GA signalling components confirm the close relationship of gymnosperms, monocotyledonous and dicotyledonous plants, as suggested from previous studies.

Conclusion:
Homologues of the GA-signalling pathway were mainly found in vascular plants. The GA signalling system may have its evolutionary molecular onset in Physcomitrella patens, where GAs at higher concentrations affect gravitropism and elongation growth.
Application of phage display to high throughput antibody generation and characterization
Authors: Schofield Darren J , Pope Anthony R , Clementel Veronica , Buckell Jenny , Chapple Susan DJ , Clarke Kay F , Conquer Jennie S , Crofts Anna M , Crowther Sandra RE , Dyson Michael R , Flack Gillian , Griffin Gareth J , Hooks Yvette , Howat William J , Kolb-Kokocinski Anja , Kunze Susan , Martin Cecile D , Maslen Gareth L , Mitchell Joanne N , O'Sullivan Maureen , Perera Rajika L , Roake Wendy , Shadbolt S Paul , Vincent Karen J , Warford Anthony , Wilson Wendy E , Xie Jane , Young Joyce L , McCafferty John 
Published: November 2007

AbstractWe have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation.
Symptom Prevalence, Intensity, and Distress in Patients With Inoperable Lung Cancer in Relation to Time of Death
Authors: Tishelman Carol , Petersson Lena-Marie , Degner Lesley F. , Sprangers Mirjam A.G. 
Published: November 2007

Purpose To examine symptom prevalence, intensity, and association with distress in patients with inoperable lung cancer (LC), using time to death as point of reference. Patients and Methods A consecutive sample of 400 patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 plus a 13-item LC-specific scale and the Thurstone Scale of Symptom Distress–Lung Cancer at six time points during the first year after diagnosis. Patients were divided into subgroups, using data from the time point closest to death (< 1; 1 to 2; > 2 to 3; > 3 to 6; > 6 to 12; and > 12 months before death) for analysis. Results More than 50% of patients in all subgroups reported problems related to physical, role, and emotional functioning; fatigue; dyspnea; and cough. In general, functional levels were lower and symptoms higher in subgroups closer to death. Notably, clinically relevant differences were also found in role and social functioning and appetite loss between the two groups furthest from death. A consistent pattern was found among the six subgroups, with breathing, pain, and fatigue rated as the symptoms most associated with distress. Conclusion High prevalence of symptoms was found in all subgroups, with higher intensity in subgroups closer to death, indicating a need for prophylactic and proactive symptom management. Less concordance was found among symptom prevalence, intensity, and association with distress in subgroups further from death. Future studies should investigate longitudinal associations between symptoms with low intensity and high distress, and examine their clinical implications.
p53 Gene and Protein Status: The Role of p53 Alterations in Predicting Outcome in Patients With Bladder Cancer
Authors: George Ben , Datar Ram H. , Wu Lin , Cai Jie , Patten Nancy , Beil Stephen J. , Groshen Susan , Stein John , Skinner Donald , Jones Peter A. , Cote Richard J. 
Published: November 2007

Purpose The p53 gene status (mutation) and protein alterations (nuclear accumulation detectable by immunohistochemistry; p53 protein status) are associated with bladder cancer progression. Substantial discordance is documented between the p53 protein and gene status, yet no studies have examined the relationship between the gene-protein status and clinical outcome. This study evaluated the clinical relationship of the p53 gene and protein statuses. Materials and Methods The complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene–sequencing chip. We compared p53 gene status, mutation site, and protein status with time to recurrence. Results The p53 gene and protein statuses show significant concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein statuses were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining the p53 gene and protein statuses stratifies patients into three distinct groups, based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), an intermediate outcome (either a mutated gene or an altered protein) and the worst outcome (a mutated gene and an altered protein). Conclusion We show that evaluation of both the p53 gene and protein statuses provides information in assessing the clinical recurrence risk in bladder cancer and that the specific mutation site may be important in assessing recurrence risk. These findings may substantially impact the assessment of p53 alterations and the management of bladder cancer.
Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Preliminary Results of GETUG-01
Authors: Pommier Pascal , Chabaud Sylvie , Lagrange Jean Leon , Richaud Pierre , Lesaunier François , Le Prise Elisabeth , Wagner Jean Philippe , Hay Meng Huor , Beckendorf Veronique , Suchaud Jean Philippe , du Chatelard Pierre Marie Pabot , Bernier Valerie , Voirin Nicolas , Perol David , Carrie Christian 
Published: November 2007

Purpose To assess the benefit and toxicity and quality-of-life (QOL) outcomes of pelvic nodes irradiation in nonmetastatic prostate carcinoma patients. Patients and Methods Between December 1998 and June 2004, 444 patients with T1b-T3, N0 pNx, M0 prostate carcinoma were randomly assigned to either pelvic and prostate radiotherapy or prostate radiotherapy only. Patients were stratified according to the prognostic factor of lymph node involvement (LNI). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for patients in the high-risk group. The pelvic dose was 46 Gy. The total dose recommended to the prostate was changed during the course of the study from 66 Gy to 70 Gy. Criteria for progression-free survival (PFS) included biologic prostate-specific antigen recurrences or a local or metastatic evolution. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group and Late Effects in Normal Tissues Subjective, Objective, Management, and Analytic scales, respectively. The QOL outcome was recorded with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30, the International Prostatic Symptom Score, and the Sexual Function Index scales. Results With a 42.1-month median follow-up time, the 5-year PFS and overall survival were similar in the two treatment arms for the whole series and for each stratified group. On multivariate analysis, low LNI risk and hormonal therapy were statistically associated with increased PFS. However, subgroup analyses based on these factors did not show any benefit for pelvic irradiation. There were no significant differences in acute and late digestive toxicities and in QOL outcomes. Conclusion Pelvic node irradiation was well tolerated but did not improve PFS.
Chemotherapy Compared With Biochemotherapy for the Treatment of Metastatic Melanoma: A Meta-Analysis of 18 Trials Involving 2,621 Patients
Authors: Ives Natalie J. , Stowe Rebecca L. , Lorigan Paul , Wheatley Keith 
Published: November 2007

Purpose To assess the effect of adding interferon-α (IFN) ± interleukin-2 (IL-2) to chemotherapy in patients with metastatic melanoma. Methods A published data meta-analysis of trials of biochemotherapy versus chemotherapy in patients with metastatic melanoma was undertaken. End points evaluated were rates of partial response (PR), complete response (CR) and overall (partial + complete) response (OR); response duration; progression-free survival; overall survival (OS); and toxicity. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to whether IFN only or IFN and IL-2 were administered in the biochemotherapy arm. Results Eighteen randomized trials were identified: 11 trials of chemotherapy ± IFN and seven trials of chemotherapy ± IFN and IL-2. More than 2,600 patients were entered onto the trials, with 555 responses and 2,039 deaths. There was a clear benefit for biochemotherapy for PR (odds ratio = 0.66; 95% CI, 0.53 to 0.82; P = .0001), CR (odds ratio = 0.50; 95% CI, 0.35 to 0.73; P = .0003) and OR (odds ratio = 0.59; 95% CI, 0.49 to 0.72; P < .00001). For OR, these benefits were significant for both the IFN (odds ratio = 0.60; 95% CI, 0.46 to 0.79; P = .0002) and IFN + IL-2 (odds ratio = 0.58; 95% CI, 0.44 to 0.77; P = .0001) subgroups. In contrast, there was no benefit overall in OS (odds ratio = 0.99; 95% CI, 0.91 to 1.08; P = .9), but there was evidence of heterogeneity of treatment effect between the individual trials (P = .006). Conclusion This meta-analysis provides a comprehensive summary of all the data currently available, and shows that although biochemotherapy clearly improves response rates, this does not appear to translate into a survival benefit.
Positron Emission Tomography for Staging of Pediatric Sarcoma Patients: Results of a Prospective Multicenter Trial
Authors: Völker Thomas , Denecke Timm , Steffen Ingo , Misch Daniel , Schönberger Stefan , Plotkin Michail , Ruf Juri , Furth Christian , Stöver Brigitte , Hautzel Hubertus , Henze Günter , Amthauer Holger 
Published: November 2007

Purpose The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18–fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients. Patients and Methods In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 ± 12 months), and histopathology and was determined by an interdisciplinary tumor board. Results FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001). Conclusion In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.
Prospective Study of a Pirarubicin, Intermediate-Dose Cytarabine, and Etoposide Regimen in Children With Down Syndrome and Acute Myeloid Leukemia: The Japanese Childhood AML Cooperative Study Group
Authors: Kudo Kazuko , Kojima Seiji , Tabuchi Ken , Yabe Hiromasa , Tawa Akio , Imaizumi Masue , Hanada Ryoji , Hamamoto Kazuko , Kobayashi Ryoji , Morimoto Akira , Nakayama Hideki , Tsuchida Masahiro , Horibe Keizo , Kigasawa Hisato , Tsukimoto Ichiro 
Published: November 2007

Purpose To evaluate a less intensive chemotherapeutic regimen specifically designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML), and to determine the prognostic factors for event-free survival. Patients and Methods Seventy-two patients with AML-DS were treated with remission induction chemotherapy consisting of pirarubicin (25 mg/m2/d for 2 days), cytarabine (100 mg/m2/d for 7 days), and etoposide (150 mg/m2/d for 3 days). Patients received four courses of intensification therapy of the same regimen. Prophylaxis for CNS leukemia was not included. Results All but two patients were younger than 4 years, and 67 of the 72 patients (93%) were diagnosed as acute megakaryoblastic leukemia (AMKL). Seventy of the 72 patients (97.2%) achieved a complete remission (CR), and the estimated 4-year event-free survival (EFS) rate was 83% ± 9%. Nine patients relapsed, and one died as a result of pneumonia during CR. Multivariate analysis revealed that the presence of monosomy 7 was a greater risk factor of adverse outcome (odds ratio = 5.67; P = .027). Conclusion A less intensive chemotherapeutic regimen produces excellent outcomes in standard-risk AML-DS patient. Risk-oriented therapy should be considered for future trials in AML-DS.
Randomized Double-Blind Trial of Prophylactic Oral Minocycline and Topical Tazarotene for Cetuximab-Associated Acne-Like Eruption
Authors: Scope Alon , Agero Anna Liza C. , Dusza Stephen W. , Myskowski Patricia L. , Lieb Jocelyn A. , Saltz Leonard , Kemeny Nancy E. , Halpern Allan C. 
Published: November 2007

Purpose To evaluate the ability of either oral minocycline, topical tazarotene or both, to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy. Patients and Methods Metastatic colorectal cancer patients preparing to initiate cetuximab were randomly assigned to receive daily oral minocycline or placebo, and to receive topical tazarotene application to either left or right side of the face. Both therapies were administered for 8 weeks. Results Forty-eight eligible patients were randomly assigned to minocycline (n = 24) or placebo (n = 24). Total facial lesion counts were significantly lower in patients receiving minocycline at weeks 1 through 4. At week 4, a lower proportion of patients in the minocycline arm reported moderate to severe itch than in the placebo arm (20% v 50%, P = .05). Facial photographs, obtained at week 4, were reviewed for rash global severity. Patients in the minocycline arm trended toward lower frequency of moderate to severe rash than patients receiving placebo (20% v 42%, P = .13). The differences in total facial lesion counts and subjectively assessed itch were diminished by week 8. Cetuximab treatment was interrupted because of grade 3 skin rash in four patients in the placebo arm, and none in the minocycline arm. There was no observed clinical benefit to tazarotene application. Tazarotene treatment was associated with significant irritation, causing its discontinuation in one third of patients. Conclusion Prophylaxis with oral minocycline may be useful in decreasing the severity of the acneiform rash during the first month of cetuximab treatment. Topical tazarotene is not recommended for management of cetuximab-related rash.