bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of resistance to chemotherapeutic drugs in human osteosarcoma cell lines largely depends on up‐regulation of clusterin/apolipoprotein J
Authors: Lourda Magda , Trougakos Ioannis P. , Gonos Efstathios S. 
Published: November 2006

AbstractClusterin/Apolipoprotein J (CLU) is differentially regulated during in vivo cancer progression. We have addressed the role of CLU during the acquisition and maintenance of human cancer cells resistance to chemotherapeutic drugs. We used two osteosarcoma (OS) cell lines, namely U‐2 OS and KH OS, and selected three generations of doxorubicin (DXR)‐resistant cells (R1, R2 and R3; resistant to 0.0035, 0.035 and 0.35 μM DXR, respectively) by continuous exposure to increasing, clinically relevant, DXR concentrations. Our studies showed that the DXR‐resistant OS cell lines were cross‐resistant to a variety of unrelated cytotoxic agents. Analysis of the CLU mRNA and protein expression levels revealed a minimal CLU up‐regulation in the U‐2 OS R2 cells and a significant, more than 4‐fold, induction in the KH OS R2 and R3 cells. Antibody‐mediated neutralization of the extracellular CLU, or silencing of CLU gene expression via small interfering RNA (siRNA) partially sensitized KH OS R2 cells to the drugs assayed. Moreover, siRNA‐mediated CLU knock down in the absence of DXR induced high levels of endogenous spontaneous apoptosis in both the parental and R2 OS cell lines. This effect was enhanced by more than 60% in the KH OS R2 cells as compared to their parental counterparts, indicating that the high CLU levels in the KH OS R2 cells are essential for survival. Overall, we suggest that CLU up‐regulation in the multi‐drug resistant OS cells relates to enhanced drug resistance. Therefore, CLU may represent a predictive marker, which correlates to response of cancer cells to chemotherapy. © 2006 Wiley‐Liss, Inc.
Whole genome tiling path array CGH analysis of segmental copy number alterations in cervical cancer cell lines
Authors: Lockwood William W. , Coe Bradley P. , Williams Ariane C. , MacAulay Calum , Lam Wan L. 
Published: November 2006

AbstractCervical cancer is the second most common malignancy in women worldwide, with high risk subtypes of human papillomavirus (HPV) constituting the major etiological agent. However, only a small percentage of women infected by the virus develop disease, suggesting that additional host genetic alterations are necessary for disease progression. In this study we examined the genomes of a panel of commonly used model cervical cancer cell lines using a recently developed whole genome tiling path array for CGH analysis. Detailed analysis of genomic profiles enabled the detection of many novel aberrations, which may have been missed by conventional cytogenetic methods. In total, 27 minimal regions of recurrent copy number alteration were identified that are potentially involved in tumorigenesis. Interestingly, fine mapping of the 3q gain, which is associated with the progression of precursor lesions to invasive cervical cancer, identified a minimal region of alteration harboring genes distinct from previous candidates. Novel regions of gene amplification, including the coamplification of both the Birc and MMP gene clusters on 11q22, were also evident. Lastly, characterization of genomic structure at sites of HPV integration identified the copy number gain of host cellular sequences between the viral‐host genomic boundaries in both SiHa and SW756, suggesting a direct role for HPV integration in the development of genetic abnormalities that initiate cervical cancer. This work represents the highest resolution look at a cervical cancer genome to date and offers definitive characterization of the alteration status of these cancer cell lines. © 2006 Wiley‐Liss, Inc.
Familial adenomatous polyposis patients have high levels of arachidonic acid and docosahexaenoic acid and low levels of linoleic acid and α‐linolenic acid in serum phospholipids
Authors: Almendingen Kari , Höstmark Arne T. , Fausa Olav , Mosdöl Annhild , Aabakken Lars , Vatn Morten H. 
Published: November 2006

AbstractFamilial adenomatous polyposis (FAP) provides a model of APC inactivation as an early genetic event for the ∼85% of colorectal cancers that develop from polyps. Abnormal fatty acid composition of tissues and serum phospholipids has been linked to cancer risk. Our aim was to describe the composition of fatty acids in serum phospholipids in 38 colectomized FAP patients as compared to 160 healthy subjects. Mean fatty acid intakes were similar between the groups. Colectomy was done on average 16 years prior to inclusion, and 18% were diagnosed with colorectal cancer at colectomy. The levels (weight %) of linoleic and α‐linolenic acid were higher among the reference subjects (difference: 3.96, 95% confidence interval (CI) = 2.87, 5.04, and difference: 0.06, 95% CI = 0.04, 0.08, respectively), and the levels of arachidonic and docosahexaenoic acid were lower (difference: −3.70, 95% CI = −4.35, −3.06, and difference: −5.26, 95% CI = −6.25, −4.28, respectively) as compared to the FAP patients (all p ≤ 0.0001). The abnormal fatty acid composition was not related to time since colectomy, intestinal reconstruction or history of colorectal cancer for any of the fatty acids assessed. Compositional differences in the fatty acid profile of serum phospholipids have not been described before in FAP patients. Further studies are needed to confirm these findings and assess clinical significances of a possible distorted fatty acid metabolism, including a potentially different dietary need of essential fatty acids. The relevance of these findings for APC induced cancers remains unclear. © 2006 Wiley‐Liss, Inc.
Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer
Authors: Slattery Martha L. , Curtin Karen , Sweeney Carol , Levin Theodore R. , Potter John , Wolff Roger K. , Albertsen Hans , Samowitz Wade S. 
Published: November 2006

AbstractIt has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population‐based case‐control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP‐high tumors. Dietary folate, vitamins B6 and B12, methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP‐high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP‐low and CIMP‐high tumors. Our results also suggested non‐CIMP pathways as well. Obese individuals were at 2‐fold increased risk of having a CIMP‐low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP‐low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B6 and B12 and methionine in a CpG island methylator phenotype. © 2006 Wiley‐Liss, Inc.
Second malignancies among survivors of germ‐cell testicular cancer: A pooled analysis between 13 cancer registries
Authors: Richiardi Lorenzo , Scélo Ghislaine , Boffetta Paolo , Hemminki Kari , Pukkala Eero , Olsen Jorgen H. , Weiderpass Elisabete , Tracey Elizabeth , Brewster David H. , McBride Mary L. , Kliewer Erich V. , Tonita Jon M. , Pompe‐Kirn Vera , Kee‐Seng Chia , Jonasson Jon G. , Martos Carmen , Brennan Paul 
Published: November 2006

AbstractWe investigated the risk of second malignancies among 29,511 survivors of germ‐cell testicular cancer recorded in 13 cancer registries. Standardized incidence ratios (SIRs) were estimated comparing the observed numbers of second malignancies with the expected numbers obtained from sex‐, age‐, period‐ and population‐specific incidence rates. Seminomas and nonseminomas, the 2 main histological groups of testicular cancer, were analyzed separately. During a median follow‐up period of 8.3 years (0–35 years), we observed 1,811 second tumors, with a corresponding SIR of 1.65 (95% confidence interval (CI): 1.57–1.73). Statistically significant increased risks were found for fifteen cancer types, including SIRs of 2.0 or higher for cancers of the stomach, gallbladder and bile ducts, pancreas, bladder, kidney, thyroid, and for soft‐tissue sarcoma, nonmelanoma skin cancer and myeloid leukemia. The SIR for myeloid leukemia was 2.39 (95% CI: 1.41–3.77) after seminomas, and 6.77 (95% CI: 4.14–10.5) after nonseminomas. It increased to 37.9 (95% CI: 18.9–67.8; based on 11 observed cases of leukemia) among nonseminoma patients diagnosed since 1990. SIRs for most solid cancers increased with follow‐up duration, whereas they did not change with year of testicular cancer diagnosis. Among subjects diagnosed before 1980, 20 year survivors of seminoma had a cumulative risk of solid cancer of 9.6% (95% CI: 8.7–10.5%) vs. 6.5% expected, whereas 20 years survivors of nonseminoma had a risk of 5.0% (95% CI: 4.2–6.0%) vs. 3.1% expected. In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role. © 2006 Wiley‐Liss, Inc.
Associations between serum carotenoids and tocopherols and type‐specific HPV persistence: The Ludwig‐McGill cohort study
Authors: Siegel Erin M. , Craft Neal E. , Duarte‐Franco Eliane , Villa Luisa L. , Franco Eduardo L. , Giuliano Anna R. 
Published: November 2006

AbstractAlthough oncogenic HPV infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to cervical lesions. Current research is focused on identifying factors associated with viral persistence and clearance, such as nutritional status. We evaluated the association between serum antioxidant nutrients (retinol, 10 carotenoids and 3 tocopherols) and type‐specific HPV persistence over 4 visits among 405 women participating in the Ludwig‐McGill cohort study. We measured circulating carotenoids and tocopherol at 4 different clinical visits for each woman. We report the results from different analytic approaches (a case–control approach at both the woman and viral level, and a prospective approach based on persistent events) that examined the association between these micronutrients and type‐specific oncogenic and nononcogenic HPV persistence. In the case–control analysis at the viral level, midcirculating levels of α‐tocopherol were inversely associated with nononcogenic HPV persistent infection (adjusted odds ratio (AOR) = 0.28, 95% CI 0.14–0.57), while high levels were marginally associated (AOR = 0.59, 95% CI 0.28–1.19). Similarly, utilizing generalized estimating equation models, circulating levels of α‐ and δ‐tocopherol in the middle or upper tertiles were inversely associated with type‐specific nononcogenic HPV persistence (AOR = 0.44, 95% CI 0.19–0.97 and AOR = 0.46, 95% CI 0.19–1.11, respectively). Our study among Brazilian women suggests that serum levels of tocopherols may be protective against nononcogenic HPV persistence. However, we did not find a strong protective effect (as hypothesized) of other serum antioxidant nutrients and type‐specific oncogenic HPV persistence measured over 4 clinical visits. © 2006 Wiley‐Liss, Inc.
Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome
Authors: Renkonen‐Sinisalo Laura , Bützow Ralf , Leminen Arto , Lehtovirta Pentti , Mecklin Jukka‐Pekka , Järvinen Heikki J. 
Published: November 2006

AbstractThe estimated lifetime risk for endometrial carcinoma (EC) in hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is 32–60%, thus supporting surveillance. The survival rate of EC patients is, however, favourable questioning the need for surveillance. Yet, the effectiveness of gynecological surveillance remains to be shown. The 2 previously published studies were based on transvaginal ultrasound (TVUS) alone. Intrauterine biopsy has not been tested in surveillance for EC in HNPCC families. The effect of gynecological surveillance was evaluated among 175 Finnish mutation carriers. During 759 person years at risk, there were 503 surveillance visits including TVUS and intrauterine biopsy of endometrium at 94% and 74% of the visits, respectively. EC occurred in 14 cases, 11 of which were diagnosed by surveillance, 8 by intrauterine biopsies. TVUS indicated only 4 EC patients but missed 6 other cases. Intrauterine sampling detected 14 additional cases of potentially premalignant hyperplasia. The stage distribution and survival tended to be more favorable in the 14 EC cases of the surveilled group (no deaths) than in the group of 83 symptomatic mutation carriers of whom 6 died of EC, but with no statistical significance. Four cases of ovarian cancer occurred but none was detected by surveillance in TVUS examinations. In conclusion, EC surveillance in HNPCC seems more effective with endometrial biopsies than with TVUS alone. A definite improvement in survival remains to be shown. The detection of early cancer stages and premalignant lesions offers the opportunity to avoid extensive adjuvant treatment. © 2006 Wiley‐Liss, Inc.
Analysis of the extracellular matrix vesicle proteome in mineralizing osteoblasts
Authors: Xiao Zhen , Camalier Corinne E. , Nagashima Kunio , Chan King C. , Lucas David A. , Cruz M. Jason de la , Gignac Michelle , Lockett Stephen , Issaq Haleem J. , Veenstra Timothy D. , Conrads Thomas P. , Beck George R. 
Published: November 2006

AbstractMany key processes central to bone formation and homeostasis require the involvement of osteoblasts, cells responsible for accumulation and mineralization of the extracellular matrix (ECM). During this complex and only partially understood process, osteoblasts generate and secrete matrix vesicles (MVs) into the ECM to initiate mineralization. Although they are considered an important component of mineralization process, MVs still remain a mystery. To better understand their function and biogenesis, a proteomic analysis of MVs has been conducted. MVs were harvested by two sample preparation approaches and mass spectrometry was utilized for protein identification. A total of 133 proteins were identified in common from the two MV preparations, among which were previously known proteins, such as annexins and peptidases, along with many novel proteins including a variety of enzymes, osteoblast‐specific factors, ion channels, and signal transduction molecules, such as 14‐3‐3 family members and Rab‐related proteins. To compare the proteome of MV with that of the ECM we conducted a large‐scale proteomic analysis of collagenase digested mineralizing osteoblast matrix. This analysis resulted in the identification of 1,327 unique proteins. A comparison of the proteins identified from the two MV preparations with the ECM analysis revealed 83 unique, non‐redundant proteins identified in all three samples. This investigation represents the first systematic proteomic analysis of MVs and provides insights into both the function and origin of these important mineralization‐regulating vesicles. J. Cell. Physiol. 210: 325–335, 2007. © 2006 Wiley‐Liss, Inc.
MicroRNAs and their regulatory roles in animals and plants
Authors: Zhang Baohong , Wang Qinglian , Pan Xiaoping 
Published: November 2006

AbstractmicroRNAs (miRNAs) are an abundant class of newly identified endogenous non‐protein‐coding small RNAs. They exist in animals, plants, and viruses, and play an important role in gene silencing. Translational repression, mRNA cleavage, and mRNA decay initiated by miRNA‐directed deadenylation of targeted mRNAs are three mechanisms of miRNA‐guided gene regulation at the post‐transcriptional levels. Many miRNAs are highly conserved in animals and plants, suggesting that they play an essential function in plants and animals. Lots of investigations indicate that miRNAs are involved in multiple biological processes, including stem cell differentiation, organ development, phase change, signaling, disease, cancer, and response to biotic and abiotic environmental stresses. This review provides a general background and current advance on the discovery, history, biogenesis, genomics, mechanisms, and functions of miRNAs. J. Cell. Physiol. 210: 279–289, 2007. © 2006 Wiley‐Liss, Inc.
Skp2‐mediated p27(Kip1) degradation during S/G2 phase progression of adipocyte hyperplasia
Authors: Auld Corinth A. , Fernandes Karishma M. , Morrison Ron F. 
Published: November 2006

Abstractp27(Kip1), an important regulator of Cdk2 activity and G1/S transition, is tightly regulated in a cell‐type and condition‐specific manner to integrate mitogenic and differentiation signals governing cell cycle progression. We show that p27 protein levels progressively declined from mid‐G1 through late‐G2 phase as density‐arrested 3T3‐L1 preadipocytes synchronously reentered the cell cycle during early stages of adipocyte differentiation. This dramatic fall in p27 protein accumulation was due, at least in part, to a decrease in protein stability. Specific inhibitors of the 26S proteasome were shown to completely block the decrease in p27 protein levels throughout G1, increase the abundance of ubiquitylated p27 protein, and inhibit G1/S transition resulting in G1 arrest. It is further demonstrated that p27 was phosphorylated on threonine 187 during S phase progression by Cdk2 and that phosphorylated p27 was polyubiquitylated and degraded. Furthermore, we demonstrate that Skp2 and Cks1 dramatically increased during S/G2 phase progression concomitantly with the maximal fall in p27 protein. Complete knockdown of Skp2 with RNA interference partially prevented p27 degradation equivalent to that observed with Cdk2 blockade suggesting that the SCFSkp2 E3 ligase and other proteasome‐dependent mechanisms contribute to p27 degradation during preadipocyte replication. Interestingly, Skp2‐mediated p27 degradation was not essential for G1/S or S/G2 transition as preadipocytes shifted from quiescence to proliferation during adipocyte hyperplasia. Finally, evidence is presented suggesting that elevated p27 protein in the absence of Skp2 was neutralized by sequestration of p27 protein into Cyclin D1/Cdk4 complexes. J. Cell. Physiol. 211: 101–111, 2007. © 2006 Wiley‐Liss, Inc.
Education or employment—choices facing young people in Kazakhstan
Authors: Kalyuzhnova Yelena , Kambhampati Uma 
Published: November 2006

AbstractThis paper considers the links between education and employment in Kazakhstan. Using a sample of 12 000 Kazakhstani households, we analyse the factors determining the choice made by young adults between education and work within a multinomial logit framework. Our results confirm that while men are more likely to work and to remain unemployed, women are actually much more likely than men to study further. The main findings of the paper are firstly, contrary to studies elsewhere in the world, the family's income level does not influence the probability of study but influences all other choices significantly. Secondly, like studies conducted on most other countries of the world, the educational status of parents significantly influences the choices made by their offspring. In addition, the regional (location) characteristics play a role in the choice of post‐compulsory education. Copyright © 2006 John Wiley & Sons, Ltd.
An unconventional IAP‐binding motif revealed by target‐assisted iterative screening (TAIS) of the BIR3‐cIAP1 domain
Authors: Kurakin Alexei , Bredesen Dale E. 
Published: November 2006

AbstractTarget‐assisted iterative screening (TAIS) has been applied to a random phage‐displayed peptide library in a search for novel ligands of the third baculovirus IAP (‘inhibitors of apoptosis’) repeat (BIR) domain of cIAP1. The peptides selected in the screen fall into two distinct specificity groups, one that conforms to a known IAP‐binding motif (IBM) and another one that reveals a novel BIR domain interacting motif, NH2‐SR(V/P)W. The biochemical profiling of selected sequences with synthetic peptides, which included alanine scanning and N‐ and C‐terminal truncations as well as competition with the Smac peptide, suggests a major energetic contribution of tryptophan at the +4 position of peptide ligands to binding and identifies the latter together with the respective pocket on the BIR domain surface as a ‘hot spot’ of the interaction. A peptide featuring the novel motif selectively binds the full‐length cIAP1 protein in cell lysates. A ‘two‐pocket’ model of BIR domain recognition mechanism is proposed as the basis of differential BIR domain interactions with different IBMs. Copyright © 2006 John Wiley & Sons, Ltd.
DENSE and HARP: Two views on the same technique of phase‐based strain imaging
Authors: Kuijer Joost P.A. , Hofman Mark B.M. , Zwanenburg Jaco J.M. , Marcus J. Tim , van Rossum Albert C. , Heethaar Rob. M. 
Published: November 2006

AbstractPurposeTo discuss differences between displacement encoding with stimulated echoes (DENSE) and the harmonic phase (HARP) in imaging and reconstruction strategies.Materials and MethodsHARP and DENSE are presented in their historical context: while the HARP method was developed from the framework of myocardial tagging, DENSE arose from the framework of stimulated echo and displacement encoding using bipolar gradients. Both techniques have evolved since their introduction, thereby becoming more similar over time and losing their distinct features. Newly introduced improvements have successfully been applied in both methods. Differences between both methods are discussed point by point.ResultsFrom this discussion it follows that almost all apparent differences are in fact nonexistent.ConclusionIn the literature, both techniques are still regarded as distinctly different techniques, where a more general treatment of the technique is justified. Once it is realized that both frameworks are easily merged, the benefits are 1) less confusion about the (dis)advantages of either technique, and 2) understanding of phase‐based strain imaging that is more general than HARP or DENSE alone. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Intravascular hematocrit layering in equilibrium phase contrast‐enhanced MR angiography of the peripheral vasculature
Authors: Wang Maisie S. , Haynor David R. , Wilson Gregory J. , Maki Jeffrey H. 
Published: November 2006

AbstractPurposeTo evaluate intravenous hematocrit (HCT) layering detected in patent calf veins that potentially simulate filling defects seen in deep venous thrombosis (DVT).Materials and MethodsFlow characteristics, vessel size, and enhancement patterns of veins with HCT layering were examined and compared with those of normal veins in vivo. Ex vivo studies were conducted with conventional and blood pool contrast agents to study the effects of MRI parameters and intrinsic variables on detecting HCT layering.ResultsHCT layering was detected in high resolution equilibrium phase images in one of six healthy subjects, and five of five patients with peripheral vascular occlusive disease (PVOD). Layering occurred only in deep veins that had significantly slower flow and larger diameter (P < 0.001) compared to normal veins. Enhancement patterns observed in vivo were similar to those found in the ex vivo study.ConclusionThe HCT layering effect in MR venography has not been previously reported, likely because delayed equilibrium phase venous imaging is not frequently performed. The use of blood pool contrast agents and high resolution equilibrium phase imaging allows intravascular HCT layering to be observed within a 30–60‐minute time frame. Several imaging characteristics that distinguish HCT layering from DVT are discussed. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.