bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paracrine inhibition of osteoblast differentiation induced by neuroblastoma cells
Authors: Granchi Donatella , Baglìo Serena Rubina , Amato Ilaria , Giunti Armando , Baldini Nicola 
Published: July 2008

AbstractThe aim of our study was to investigate whether the defective function of osteogenic cells induced by neuroblastoma might play a role in the development of skeletal metastases. This mechanism has been extensively demonstrated for multiple myeloma, in which the blockage of osteoblast differentiation has been ascribed to the inhibitors of canonical Wingless pathway (Wnt), namely Dickkopf 1 (Dkk1). Our purpose was to verify if neuroblastoma cells derived from bone marrow metastases (SH‐SY5Y, LAN1) or primaries (NB100, CHP212) hamper the differentiation of mesenchymal stem cells (hMSCs) into osteoblasts in a paracrine manner, and to test whether this ability depends on Dkk1 activity. We found that all neuroblastoma cells increased the proliferation of hMSCs collected from pediatric‐aged donors, with a corresponding decrease in osteoblast differentiation markers, including alkaline phosphatase (ALP), analyzed as gene expression, enzymatic activity and number of ALP‐positive colony forming units, osteoprotegerin (OPG) release, OPG and osteocalcin gene‐expression. Dkk1 mRNA and protein were detectable in all cell lines, and the use of neutralizing anti‐Dkk1 antibody reversed the effects induced by SH‐SY5Y cells. Taken together, our results confirm that neuroblastoma hinders osteoblastogenesis, and that Dkk1 release seems to play a crucial role in blocking the differentiation of osteoprogenitor cells, though the ability to promote osteoclast activation remains an essential requirement for the development of skeletal metastases. Finally, our findings suggest that strategies regulating Wnt signaling and Dkk1 activity could be considered for adjuvant therapies in neuroblastoma metastasizing to the skeleton. © 2008 Wiley‐Liss, Inc.
CHFR expression is preferentially impaired in smoking‐related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes
Authors: Takeshita Masafumi , Koga Takaomi , Takayama Koichi , Kouso Hidenori , Nishimura‐Ikeda Yuko , Yoshino Ichiro , Maehara Yoshihiko , Nakanishi Yoichi , Sueishi Katsuo 
Published: July 2008

AbstractLoss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, has been detected in a variety of solid tumors. Recently, CHFR has been revealed to ensure chromosomal stability by controlling the expression level of Aurora‐A in vitro. However, the frequency of aberrant expression of these proteins and the association with clinicopathologic parameters remain poorly defined in nonsmall‐cell lung cancer (NSCLC). In this study, we investigated the immunohistochemical protein expression of CHFR and Aurora‐A in 157 NSCLC cases and evaluated the association between clinicopathologic parameters statistically. The relationship between CHFR protein and mRNA levels and the association between this relationship and promoter methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC. Overexpression of Aurora‐A and reduced expression of CHFR were found in 94 cases (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly correlated with tumor differentiation and size. Moreover, diminished CHFR expression was significantly associated with smoking‐related squamous cell carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expression. In conclusion, our results suggest the aberrant expression of Aurora‐A and/or of CHFR contributed to the increase in the malignant potential of NSCLC. We also revealed that CHFR expression was predominantly impaired in smoking‐related squamous cell carcinoma and might be a useful prognostic marker in NSCLC. © 2008 Wiley‐Liss, Inc.
Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables
Authors: Afaq Farrukh , Zaman Najia , Khan Naghma , Syed Deeba N. , Sarfaraz Sami , Zaid Mohammad Abu , Mukhtar Hasan 
Published: July 2008

AbstractInhibitors of the epidermal growth factor receptor (EGFR) have generated considerable hope for cancer treatment, specifically for lung and breast cancers. Therefore, identification of a natural, nontoxic agent(s) as an inhibitor of EGFR is of considerable importance. Delphinidin, an anthocyanidin present in pigmented fruits and vegetables, possesses potent antioxidant and antiproliferative properties. In our study, employing EGFR positive breast cancer AU‐565 cells and immortalized MCF‐10A cells, we evaluated the effect of delphinidin on EGFR and its downstream signaling pathways. Delphinidin (5–40 μM; 3 hr) treatment of both AU‐565 cells and MCF‐10A cells inhibited the (i) phosphorylation of EGFR, (ii) activation of PI3K, (iii) phosphorylation of AKT and MAPK. Further, delphinidin treatment of AU‐565 cells inhibited EGF‐induced autophosphorylation of EGFR, AKT and MAPK, activation of PI3K and cell invasion. We then compared the growth inhibitory effects of delphinidin (5–40 μM; 48 hr), and found that it resulted in a decrease in cell growth of AU‐565 and MCF‐10A cells but had only minimal effects on normal mammary epithelial 184A1 cells. Treatment of AU‐565 cells with delphinidin resulted in (i) induction of apoptosis, (ii) cleavage of PARP protein, (iii) activation of caspase‐3 and (iv) downregulation of Bcl‐2 with an increase in the expression of Bax. In summary, our study identifies a naturally occurring dietary agent delphinidin as an effective inhibitor of EGFR signaling in breast cancer cells. We suggest that delphinidin could be developed as an agent for the management of EGFR positive human cancers. © 2008 Wiley‐Liss, Inc.
Trends in incidence and mortality of thyroid carcinoma in The Netherlands between 1989 and 2003: Correlation with thyroid fine‐needle aspiration cytology and thyroid surgery
Authors: Netea‐Maier Romana T. , Aben Katja K.H. , Casparie Mariel K. , den Heijer Martin , Grefte Johanna M.M. , Slootweg Piet , Hermus Ad 
Published: July 2008

AbstractA persistent increase in incidence of thyroid carcinoma (TC) has been reported worldwide. The aim of our study was to assess trends in incidence and mortality of TC in The Netherlands between 1989 and 2003 and to examine whether these trends correlate with changes in diagnostic practices such as changes in the number of fine needle aspiration biopsies (FNAB) and/or thyroid surgeries. Population‐based incidence and mortality data were retrieved from the Netherlands Cancer Registry. Data concerning FNAB and thyroid surgeries were obtained through the nationwide network and registry of histo‐ and cytopathology in The Netherlands (PALGA). Overall, the incidence of TC remained unchanged. However, there was a slight increase in incidence of papillary TC of 2.1% per year (p < 0.001) particularly in stage I tumors, possibly, in part, because of a marked increase in use of FNAB. Appropriate iodine intake, reduced radiation exposure and a more conservative diagnostic approach toward asymptomatic thyroid nodules may explain why this increase is less pronounced compared to other countries. Incidence of other subtypes of TC decreased (follicular TC, 1.3% per year, p = 0.02 and anaplastic TC, 7.1% per year, p = 0.006) or remained unchanged (medullary TC). The number of FNABs per year progressively increased from 1,093 in 1989 to 4,123 in 2003, whereas the number of thyroid surgeries decreased from 3,419 in 1989 to 2,825 in 2003. The mortality rates decreased by 2.3% per year (p = 0.01). The decrease in incidence of both follicular and anaplastic TC is assumed to be largely responsible for the decrease in TC mortality rates. © 2008 Wiley‐Liss, Inc.
Host and viral factors in relation to clearance of human papillomavirus infection: A cohort study in Taiwan
Authors: Lai Chyong‐Huey , Chao Angel , Chang Chee‐Jen , Chao Fang‐Yu , Huang Huei‐Jean , Hsueh Swei , Lin Cheng‐Tao , Cheng Hui‐Hsin , Huang Chu‐Chun , Yang Jung‐Erh , Wu Tzu‐I , Chou Hung‐Hsueh , Chang Ting‐Chang 
Published: July 2008

AbstractHuman papillomavirus (HPV) persistence is essential for cervical cancer development. We accrued nested‐cohort subjects from a population‐based study to investigate the host and viral factors related to outcome of HPV infection. Women (age ≥ 30 years old) with HPV‐positive but normal cytology and negative colposcopy were invited to participate. After signing informed consent, every participant completed a structured questionnaire and had 6‐monthly follow‐ups of Pap smear, HPV testing and colposcopy. Total and type‐specific HPV clearance rates as well as host and viral factors associated with clearance in 3‐year longitudinal follow‐up were analyzed. Adjusted hazard ratios (HRs) of progression to ≥ cervical intraepithelial neoplasia (CIN) 2 according to baseline HPV of the women with normal cytology were calculated from national registry database. Among the 626 eligible women, 526 (median age 47, 29–75) were enrolled and 412 returned for follow‐up at least once. The median follow‐up of enrolled subjects was 23 months (range 6.8–39). The 3‐year cumulative total HPV clearance rate was 49.0% (95% confidence interval [CI]: 43.3–54.7%). The median 3‐year cumulative type‐specific HPV clearance rate was 50.0% (range 0–100.0%) with a median time to clearance of 12.4 months (6.4–24.5). Older age was associated with significantly decreased total HPV clearance and decreased type‐specific clearance in HPV‐18 and ‐53, while high viral load was associated with decreased total and type‐specific clearance. After adjusting confounding variables, the HR of developing ≥CIN2 in baseline HPV‐positive women was 34.0‐fold (95% CI: 15.5–74.7) as compared to HPV‐negative women. © 2008 Wiley‐Liss, Inc.
The enhancer of zeste homolog 2 gene contributes to cell proliferation and apoptosis resistance in renal cell carcinoma cells
Authors: Wagener Nina , Holland Daniela , Bulkescher Julia , Crnković‐Mertens Irena , Hoppe‐Seyler Karin , Zentgraf Hanswalter , Pritsch Maria , Buse Stephan , Pfitzenmaier Jesco , Haferkamp Axel , Hohenfellner Markus , Hoppe‐Seyler Felix 
Published: July 2008

AbstractThe enhancer of zeste homolog 2 (EZH2) gene has been recently linked to human malignancies where it may serve as a new target for cancer therapy. Here, we analyzed EZH2 expression in primary renal cell carcinoma (RCC) specimens and in nontumorous tissue samples from adult kidney. EZH2 transcripts were detectable in all RCC specimens examined. Expression levels were significantly higher in tumor tissue (p ≤ 0.0001) than in samples from normal adult kidney. Moreover, inhibition of endogenous EZH2 expression in RCC cell lines by RNA interference (RNAi) led to reduced proliferation and increased apoptosis in RCC cells. These data show that EZH2 is overexpressed in RCC. Furthermore, they indicate that the EZH2 gene plays a role for both the proliferation and the apoptosis resistance of RCC cells. Targeted inhibition of EZH2 could therefore represent a novel strategy to improve the therapeutic response of RCC. © 2008 Wiley‐Liss, Inc.
Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative diseases
Authors: Teofili Luciana , Martini Maurizio , Cenci Tonia , Guidi Francesco , Torti Lorenza , Giona Fiorina , Foà Robin , Leone Giuseppe , Larocca Luigi Maria 
Published: July 2008

AbstractIn polycythemia vera (PV) and essential thrombocythemia (ET) specific JAK2 mutations constitutively activate the JAK‐STAT pathway, explaining biologic findings such as endogenous erythroid colony (EECs) growth or PRV‐1 RNA overexpression. Since these markers are detected also in JAK2 wild type patients, we hypothesized that, in these cases, the activation of the JAK‐STAT pathway could be produced by a deregulation of the suppressor of cytokine signaling (SOCS) protein system. Eighty‐one patients with PV and ET (53 adults and 28 children) were investigated for the methylation status of the SOCS‐1, SOCS‐2 and SOCS‐3 CpG islands and for several myeloproliferative markers (including JAK2 and MPL mutations and clonality of hematopoiesis). SOCS‐1 or SOCS‐3 hypermethylation was identified in 23 patients and was associated with a significant decrease of SOCS‐1 or SOCS‐3 RNA and protein levels. The gene expression was restored by exposing cells to the demethylating agent 2‐deoxyazacytidin. Interestingly, SOCS‐1 or SOCS‐3 hypermethylation was detected in 6 female patients, proved negative for JAK2 or MPL mutations and exhibiting monoclonal hematopoiesis. In conclusion, SOCS‐1 or SOCS‐3 hypermethylation can activate the JAK‐STAT signaling pathway in alternative or together with JAK2 mutations. These alterations might represent a potential therapeutic target. © 2008 Wiley‐Liss, Inc.
New cancer susceptibility loci: Population and familial risks
Authors: Hemminki Kari , Försti Asta , Lorenzo Bermejo Justo 
Published: July 2008

AbstractThe recent large genotyping studies have identified a new repertoire of cancer susceptibility genes and loci which are characterized by common risk alleles and low relative risks. Because of these properties, these loci explain a much larger proportion of the etiology of the particular cancers, described by the population attributable fraction (PAF), than of their familial risks (FRRs). For breast cancer, the 9 established loci gave a joint PAF of >60%, but explaining only some 8% of the empirical FRR. For prostate cancer, 6 independent loci at chromosome 8q conferred a joint PAF of 35% but the loci explained no more than 1.9% of the empirical excess familial risks. For colorectal cancer, the contributions of the 2 identified loci to PAF and FRR were somewhat lower. The genome‐wide array platforms have been built for common variants, constraining the results to variants with high PAFs and low FRRs. However, the common variants are likely to tag rarer causative variants with much higher FRRs. The detected loci are noncoding and the underlying genetic mechanisms have not been worked out. The data suggest, in spite of the reservations for combining data on PAFs across populations, that the published first‐generation genome‐wide scans on breast, prostate and colorectal cancers have made successful inroads into genomics of common cancers, yet leaving the mechanisms to be explained. © 2008 Wiley‐Liss, Inc.
Identification of truncated chemokine receptor 7 in human colorectal cancer unable to localize to the cell surface and unreactive to external ligands
Authors: Na Il‐Kang , Busse Antonia , Scheibenbogen Carmen , Ghadjar Pirus , Coupland Sarah Ellen , Letsch Anne , Loddenkemper Christoph , Stroux Andrea , Bauer Sandra , Thiel Eckhard , Keilholz Ulrich 
Published: July 2008

AbstractChemokine receptors are thought to be involved in the process of cancer metastases. When investigating cell lines and tissues from colorectal cancer (CRC), the CCR7 protein unexpectedly was confined to the cytoplasm and not present on the cell surface. This study investigated at the DNA, mRNA and protein level, the mechanism and the consequences of the failure of CCR7 to localize to the cell membrane. In all 15 CRC cell lines tested, no surface CCR7 was detected and no chemotactic response was elicited upon in‐vitro exposure to CCR7 chemokine ligands (CCL) 19 and CCL21. Integrity of CCR7 DNA and mRNA was examined with respect to signal peptide expression in cell lines and CRC tissues by real‐time RT‐PCR and sequencing. Nine of 15 CRC cell lines and 8 of 14 CRC tissues revealed a truncated CCR7 mRNA species containing various incomplete signal peptide encoding sequences, while the corresponding DNA was intact. These results indicate in CRC frequent alternative splicing or post‐transcriptional mRNA modification resulting in a CCR7 molecule lacking an intact signal peptide prohibiting membrane translocation. Further studies would be necessary to identify a potential intracellular role of the truncated CCR7, abundantly present in the cytoplasm. © 2008 Wiley‐Liss, Inc.
Water intake and bladder cancer risk in Los Angeles County
Authors: Jiang Xuejuan , Castelao Jose E. , Groshen Susan , Cortessis Victoria K. , Shibata Darryl K. , Conti David V. , Gago‐Dominguez Manuela 
Published: July 2008

AbstractThe overall evidence of an association between fluid intake and bladder cancer is not entirely consistent. We examined the fluid intake‐bladder cancer relationship in the Los Angeles bladder cancer case‐control study. A total of 1,586 cases and their age‐, sex‐, and race‐matched neighborhood controls were interviewed in‐person from 1987 to 1999. Information on total fluid intake was derived from the consumption of specific fluids including water, coffee, tea, alcohol, milk, juice, hot chocolate and soda. Total fluid intake was not associated with bladder cancer. Daily water intake was associated with a slight decrease in bladder cancer risk, with the protection more pronounced among women (p for trend = 0.039) than among men (p for trend = 0.62). Compared to drinking <1 glass of water per day, drinking ≥6 glasses/day was associated with 0.91 (95% confidence interval, 0.67–1.22) times the risk of bladder cancer among all subjects, 0.94 (0.67–1.32) times the risk among men, and 0.69 (0.36–1.33) times the risk among women. The water intake‐bladder cancer association also seemed to be modified by daytime urination frequency with significant inverse association among subjects who urinated ≥6 times/day (p for trend = 0.015), but not among those who urinated less frequently. Similarly, the protection from water intake was confined to women who did not experience nocturia and to men who did. Results from our study suggest that water intake may be associated with a slight reduction in bladder cancer risk. © 2008 Wiley‐Liss, Inc.
Effect of hysteresis and rainfall intensity on finger dynamics
Authors: Ma Kuo‐Chen , Tan Yih‐Chi , Chen Chu‐Hui 
Published: July 2008

AbstractThe purpose of this paper is to present sand‐box experiments and a hysteresis model to explain the formation and hydraulic properties of fingered flow. Previous researches have found that a fingered path persists over long periods of constant infiltration; hysteresis could be an important factor. In this paper, a major point is to utilize the boundary and series internal scanning curves of the hysteresis model derived by Huang et al. (2005) to clearly obtain the variations between soil water content (θ) and matric suction head (ψ). The hydraulic properties of fingered flow are also acquired. For the application of the model in the field, the hysteresis curves derived by Hogarth et al. (1988) are compared. Experimental results verified that both hysteresis models and the present soil water content concept model of fingered flow can be adequately applied in field tests. We attempted to use digital image analysis to visualize and determine soil water content of fingered flow easily and quickly. The initial velocity and width of fingered flow were not constant under consistent rainfall intensity. The present concept model showed the matric suction head is uniform between different soil water content sharply in the horizontal direction. Nonuniform soil water content existed even when the potential was horizontally equalized. Copyright © 2008 John Wiley & Sons, Ltd.
Assessment of wheat and maize water productivities and production function for cropping system decisions in arid and semiarid regions
Authors: Dehghanisanij Hossein , Nakhjavani Mohammad M. , Tahiri Adel Zeggaf , Anyoji Hisao 
Published: July 2008

AbstractThe great challenge of the agricultural sector in countries located in arid and semiarid regions faced with severe water scarcity is to produce more food from less water. This may be achieved by increasing the crop water productivity (WP). Based on experiments conducted in different regions of Iran, it was found that the range of wheat WP was greater than that reported earlier by the FAO. The maize WP was high in the northwestern regions of Iran and less in the southwest. The wide ranges of WP (0.5–1.8 kg m−3 for wheat and 0.3–2.3 kg m−3 for maize) indicate tremendous opportunities for increasing agricultural production with less water. The variability of crop WP can be ascribed to climate, cropping calendar, soil characteristics, and irrigation water management. Wheat and maize WP of 1.5 and 1.7 kg m−3 were recommended as an optimum level to be considered in the cropping system of potential regions. Irrigation water applied for an optimum level of wheat and maize WP was about 2650 and 5900 m3 ha−1, respectively. The maximum wheat WP occurred under deficit irrigation, while for maize it was measured under full irrigation. Regions with higher annual rainfall and high silt content in soil were more productive under deficit irrigation management. Copyright © 2008 John Wiley & Sons, Ltd.
A study of spatial variation of discharge coefficient in broad‐crested inclined side weirs
Authors: Aghayari Fiaz , Honar Tooraj , Keshavarzi Alireza 
Published: July 2008

AbstractThe side weir is a hydraulic structure that is widely used in irrigation and drainage networks and water treatment plants. To estimate the outflow over a rectangular broad‐crested side weir, the discharge coefficient in the side weir equation needs to be determined. In this study, a comprehensive laboratory study including 240 tests was conducted in a physical model under subcritical flow conditions. The variation of discharge coefficient along the side weir was investigated in relation to height, width and slope of side weir. Furthermore the data of experimental tests were statistically analysed. As a result, a mathematical model for computation of the spatial discharge coefficient is presented in this study. The presented mathematical model enables accurate estimation of discharge coefficient along the side weir when compared with the measured data under subcritical flow conditions. Additionally, in comparison with overall discharge coefficient models, the developed model estimates a relatively accurate spatial discharge coefficient for the side weir. Additionally, to equalize the flow depth along the side weir, some relationships were proposed in this paper. Copyright © 2008 John Wiley & Sons, Ltd.