bluuebunny/crossref_metadata_2025 huggingface dataset:
An in vitro model for de‐ and remyelination using lysophosphatidyl choline in rodent whole brain spheroid cultures
Authors: Vereyken E. J. F. , Fluitsma D. M. , Bolijn M. J. , Dijkstra C. D. , Teunissen C. E.
Published: February 2009

The process of demyelination occurring in diseases as multiple sclerosis is usually investigated in animal models. A major drawback of animal models is that only one condition can be tested per animal, necessitating many animals and systemic effects are factors to be considered. The aim of the study was to develop a reproducible in vitro model for de‐ and remyelination using whole brain spheroid cultures and lysophosphatidyl choline (LPC). In spheroid cultures, single cell suspensions of embryonic day 15 rodent brain cells reaggregate under constant rotation. Three‐dimensional contacts form between the central nervous system cell types present. Multilayered myelin is maximal in four‐week old cultures. A week of repeated exposure to LPC led to 30% loss of MBP protein concentration and 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase activity measurements in both rat and mouse spheroids and 56% loss in the number of myelin sheets, with partial remyelination after a week of recovery. The number of dividing cells was increased after LPC exposure and oligodendrocytes were shown to be among the dividing cells. Microglia and astrocytes were not affected and neurons were relatively spared. This suggests that LPC toxicity is specific for myelin and oligodendrocytes. LPC toxicity could be decreased using cholesterol and simvastatin, suggesting that LPC works through altering membrane composition. Thus, in different rodent species and using different read‐outs, we could reproducibly show de‐ and remyelination in spheroid cultures after LPC exposure. This model for demyelination with potential for remyelination offers possibilities for testing novel therapies and studying mechanisms of remyelination. © 2009 Wiley‐Liss, Inc.
Hospital type and patient outcomes: an empirical examination using AMI readmission and mortality records
Authors: Jensen Paul H. , Webster Elizabeth , Witt Julia
Published: February 2009

This paper investigates whether there are differences in patient outcomes across different types of hospitals using patient‐level data on readmission and mortality associated with acute myocardial infarction (AMI). Hospitals are grouped according to their ownership type (private, public teaching, public non‐teaching) and their location (metropolitan, country and remote country). Using data collected from 130 Victorian hospitals on 19 000 patients admitted to a hospital with their first AMI between January 2001 and December 2003, we consider how the likelihood of unplanned re‐admission and mortality varies across hospital type. We find that there are significant differences across hospital types in the observed patient outcomes – private hospitals persistently outperform public hospitals. Copyright © 2009 John Wiley & Sons, Ltd.
How do physician assessments of patient preferences for colorectal cancer screening tests differ from actual preferences? A comparison in Canada and the United States using a stated‐choice survey
Authors: Marshall Deborah A. , Johnson F. Reed , Kulin Nathalie A. , Özdemir Semra , Walsh Judith M. E. , Marshall John K. , Van Bebber Stephanie , Phillips Kathryn A.
Published: February 2009

Background: Patient preferences can affect colorectal cancer (CRC) screening test use. We compared utility‐based preferences for alternative CRC screening tests from a stated‐preference discrete‐choice survey of the general population and physicians in Canada and the United States.

Methods: General population respondents (Canada, n=501; US, n=1087) participated in a survey with 12 choice scenarios and 9 CRC screening test attributes. Physicians (n=100, both Canada and US) reported expected patient preferences. We estimated relative importance of attributes using bivariate probit regression analysis and calculated willingness‐to‐pay for various CRC screening tests.

Results: In 28 and 31% of scenarios, Canadian and US respondents, respectively, chose no screening over a hypothetical test. Canadian (45%) and US (46%) physicians expected patients to choose no screening more often. For all groups the most important attribute was sensitivity, but physicians' perception of patients' preferences are significantly different from actual preferences. Other key attributes are those related to test performance or the testing process. Fecal DNA, colonoscopy, and virtual colonoscopy were the most preferred tests by all groups, but respondents were willing‐to‐pay more than physicians predicted.

Conclusion: Physicians' perception of patients' preferences are quite different from those of the general population. However, among general population and physicians, Canadian and US preferences were similar. Copyright © 2009 John Wiley & Sons, Ltd.
Physician's production of primary care in Ontario, Canada
Authors: Sarma Sisira , Devlin Rose Anne , Hogg William
Published: February 2009

This paper examines the factors affecting the number of patient visits per week reported by family physicians in Ontario. The way that a physician is paid is potentially endogenous to the number of patients seen per week, thus an instrumental variable method of estimation is employed to account for the endogeneity bias. Once account is taken of the endogeneity of remuneration as well as relevant physician and practice characteristics, the estimated elasticity of output with respect to hours worked is 0.74; 0.68 in group practices and 0.82 in solo practices. Physicians paid on a non‐fee‐for‐service (NFFS) conduct 15–31% fewer patient visits per week in comparison to those paid under an FFS scheme. Certain patient populations in practices affect patient visits in important ways, as do a number of physician and practice characteristics. Copyright © 2009 John Wiley & Sons, Ltd.
A game of two halves? Incentive incompatibility, starting point bias and the bidding game contingent valuation method
Authors: McNamee Paul , Ternent Laura , Gbangou Adjima , Newlands David
Published: February 2009

The bidding game (BG) method of contingent valuation is one way to increase the precision of willingness to pay (WTP) estimates relative to the single dichotomous choice approach. However, there is evidence that the method may lead to incentive incompatible responses and be associated with starting point bias. While previous studies in health using BGs test for starting point bias, none have also investigated incentive incompatibility. Using a sample of respondents resident in Burkina Faso, West Africa, this paper examines whether the BG method is associated with both incentive incompatibility and starting point bias. We find evidence for both effects. However, average WTP values remained largely unaffected after accounting for both factors in multivariate analyses. The results suggest that the BG method is an acceptable technique in settings where prices for goods are flexible. Copyright © 2009 John Wiley & Sons, Ltd.
Beneficiary price sensitivity in the Medicare prescription drug plan market
Authors: Frakt Austin B. , Pizer Steven D.
Published: February 2009

The Medicare stand‐alone prescription drug plan (PDP) came into existence in 2006 as part of the Medicare prescription drug benefit. It is the most popular plan type among Medicare drug plans and large numbers of plans are available to all beneficiaries. In this article we present the first analysis of beneficiary price sensitivity in the PDP market. Our estimate of elasticity of enrollment with respect to premium, −1.45, is larger in magnitude than has been found in the Medicare HMO market. This high degree of beneficiary price sensitivity for PDPs is consistent with relatively low product differentiation, low fixed costs of entry in the PDP market, and the fact that, in contrast to changing HMOs, beneficiaries can select a PDP without disrupting doctor–patient relationships. Published in 2009 by John Wiley & Sons, Ltd.
XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital‐based case‐control study
Authors: Zhou Keke , Liu Yanhong , Zhang Haishi , Liu Hongliang , Fan Weiwei , Zhong Yu , Xu Zhonghui , Jin Li , Wei Qingyi , Huang Fengping , Lu Daru , Zhou Liangfu
Published: February 2009

In mammalian cells, X‐ray repair cross‐complementing group3 (XRCC3) plays an important role in the DNA double‐strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in the XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to gliomas. In this study, we used a haplotype‐based approach to investigate whether 4 tagging single nucleotide polymorphisms of the XRCC3 gene are associated with risk of gliomas in 771 glioma patients and 752 cancer‐free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, and haplotype associations were estimated using Haplo.Stat. After adjustment for age and sex, the variant G allele of rs861530 and T allele of rs3212092 were significantly associated with an increased risk of gliomas (AG/GG versus AA: adjusted OR = 1.44, 95% CI = 1.15–1.80, p = 0.001 and CT/TT versus CC: adjusted OR = 1.66, 95% CI = 1.12–2.46, p = 0.013, respectively). Consistent with these results, XRCC3 haplotype “GGCC” containing rs861530 G allele and haplotype “AGTC” containing rs3212092 T allele were also significantly associated with an elevated risk of gliomas compared with the common haplotype “AGCC” (adjusted OR = 1.35, 95% CI = 1.14–1.58, p = 0.000 and adjusted OR = 1.67, 95% CI = 1.11–2.52, p = 0.015, respectively). Our results suggest that common genetic variants in the XRCC3 gene may modulate glioma risk. © 2009 UICC
Lysyl oxidase‐like 2 promotes migration in noninvasive breast cancer cells but not in normal breast epithelial cells
Authors: Hollosi Peter , Yakushiji Jana K. , Fong Keith S.K. , Csiszar Katalin , Fong Sheri F.T.
Published: February 2009

A growing number of studies indicate the importance of the lysyl oxidase family in the promotion of epithelial neoplasms towards their more aggressive forms. However, the role of individual family members in carcinoma progression has yet to be ascertained. In this study, we analyzed LOXL2 expression in malignantly transformed MCF‐7 and normal MCF‐10A mammary epithelial cell line clones stably transduced with LOXL2 in vitro, and in normal and cancerous breast tissue samples in vivo. We found LOXL2 to be catalytically active in both MCF‐7 and MCF‐10 clones. LOXL2 overexpression promoted a more mesenchymal morphology in both cell types, but LOXL2‐induced increase in migratory ability could only be established in MCF‐7 clones. We demonstrated altered localization of the LOXL2 protein in breast cancer tissue compared to normal mammary tissue, and altered localization and processing of LOXL2 protein in breast cancer cell lines compared to normal cell lines, which may allow LOXL2 to interact with different intra and extracellular components during tumor progression. Results support the role of LOXL2 in selectively promoting a metastatic phenotype in breast tumor cells. Additional data suggest epigenetic molecular mechanisms in tumor specific regulation of LOXL2 expression that could be explored as a molecular target in the prevention of breast cancer progression. © 2009 UICC
Risk of liver cancer and exposure to organic solvents and gasoline vapors among Finnish workers
Authors: Lindbohm Marja‐Liisa , Sallmén Markku , Kyyrönen Pentti , Kauppinen Timo , Pukkala Eero
Published: February 2009

We investigated the association between exposure to various groups of solvents and gasoline vapors and liver cancer. A cohort of economically active Finns born between 1906 and 1945 was followed up during the period 1971–1995. The incident cases of primary liver cancer (n = 2474) were identified in a record linkage with the Finnish Cancer Registry. Occupations from the 1970 census were converted to exposures using a job‐exposure matrix. Cumulative exposure was calculated as the product of estimated prevalence, level and duration of exposure, and we used Poisson regression to calculate the relative risks (RR). Among the occupations entailing exposure to organic solvents, an elevated liver cancer incidence was observed in male printers, and varnishers and lacquerers. Among men, the risk was increased in the highest exposure category of aromatic hydrocarbons [RR 1.77, 95% confidence interval (CI) 1.30–2.40], aliphatic/alicyclic hydrocarbons (RR 1.47, 95% CI 0.99–2.18), chlorinated hydrocarbons (RR 2.65, 95% CI 1.38–5.11) and “other solvents” (RR 2.14, 95% CI 1.23–3.71). Among women, the risk was increased for the group “other solvents” that includes mainly alcohols, ketones, esters and glycol ethers (RR 2.73, 95% CI 1.21–6.16). Our finding of an increased risk among workers exposed to chlorinated hydrocarbons is in line with several earlier studies on trichloroethylene. The results also suggest a link between exposure to other types of solvents and the risk of liver cancer. The possibility that alcohol consumption contributes to the observed risks cannot be totally excluded. © 2009 UICC
Glycemic load, glycemic index and breast cancer risk in a prospective cohort of Swedish women
Authors: Larsson Susanna C. , Bergkvist Leif , Wolk Alicja
Published: February 2009

High‐glycemic load diets have been hypothesized to increase the risk of breast cancer but epidemiologic studies have yielded inconsistent findings. We examined the associations of carbohydrate intake, glycemic index and glycemic load with risk of overall and hormone receptor‐defined breast cancer in the Swedish Mammography Cohort, a population‐based cohort of 61,433 women who completed a food frequency questionnaire at enrollment in 1987–1990. During a mean follow‐up of 17.4 years, we ascertained 2,952 incident cases of invasive breast cancer. Glycemic load but not carbohydrate intake or glycemic index was weakly positively associated with overall breast cancer risk (p for trend = 0.05). In analyses stratified by estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors, we observed statistically significant positive associations of carbohydrate intake, glycemic index and glycemic load with risk of ER+/PR− breast cancer; the multivariate relative risks comparing extreme quintiles were 1.34 [95% confidence interval (CI) = 0.93–1.94; p for trend = 0.04] for carbohydrate intake, 1.44 (95% CI = 1.06–1.97; p for trend = 0.01) for glycemic index and 1.81 (95% CI = 1.29–2.53; p for trend = 0.0008) for glycemic load. No associations were observed for ER+/PR+ or ER−/PR− breast tumors. These findings suggest that a high carbohydrate intake and diets with high glycemic index and glycemic load may increase the risk of developing ER+/PR− breast cancer. © 2009 UICC
Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case–referent study
Authors: Holl Katsiaryna , Lundin Eva , Surcel Heljä‐Marja , Grankvist Kjell , Koskela Pentti , Dillner Joakim , Hallmans Göran , Wadell Göran , Olafsdottir Gudridur H. , Ögmundsdottir Helga M. , Pukkala Eero , Lehtinen Matti , Stattin Pär , Lukanova Annekatrin
Published: February 2009

According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case–referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case‐index mother pair, three or four matched referent‐referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06–0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2–12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98–1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. © 2009 UICC
Fiber diffraction of skin and nails provides an accurate diagnosis of malignancies
Authors: James Veronica J.
Published: February 2009

An early diagnosis of malignancies correlates directly with a better prognosis. Yet for many malignancies there are no readily available, noninvasive, cost‐effective diagnostic tests with patients often presenting too late for effective treatment. This article describes for the first time the use of fiber diffraction patterns of skin or fingernails, using X‐ray sources, as a biometric diagnostic method for detecting neoplastic disorders including but not limited to melanoma, breast, colon and prostate cancers. With suitable further development, an early low‐cost, totally noninvasive yet reliable diagnostic test could be conducted on a regular basis in local radiology facilities, as a confirmatory test for other diagnostic procedures or as a mass screening test using suitable small angle X‐ray beam‐lines at synchrotrons. © 2009 UICC
Roles of clusterin in progression, chemoresistance and metastasis of human ovarian cancer
Authors: Wei Li , Xue Tao , Wang Jian , Chen Biliang , Lei Yingfeng , Huang Yanhong , Wang Hongying , Xin Xiaoyan
Published: February 2009

Clusterin (CLU) is a multivalent glycoprotein with ubiquitous tissue distribution. To address the possible differential functional roles assumed by different isoforms of CLU in the progression of human ovarian cancer, we constructed 2 human ovarian cancer cell models that represent examples of contradistinctive CLU expression levels. One is constitutively overexpressing different clusterin isoforms in SKOV3 cells by transfection of the 3 different expression vectors, another is silencing the intrinsically expressing clusterin in cisplatin‐resistant human A2780‐cis(CP70) tumor cells with the usage of shRNA‐mediated CLU gene silencing. Then, the different cellular localization, biological effects, and functional roles played in tumor progression and drug resistances were studied. We found that (i) in the distinct cellular contexts of human ovarian carcinoma SKOV3 and CP70 cells assayed, sCLU is a central molecule in cell homeostasis that functions as a cytoprotective protein, whereas nCLU is proapoptotic; (ii) In SKOV3 cells, nuclear localization of the truncated CLU is NLS dependent, without which the pnCLU protein was sequestrated in cytoplasm to prevent cytotoxicity. (iii) sCLU plays a significant role in the development of the chemoresistance phenotype in ovarian cancer cells. Moreover, with the CLU‐specific shRNA oligonucleotides, we successfully sensitized cells for chemotherapy, and inhibited cells' proliferation, migration and invasion. Collectively, our results reveal that, CLU gene expression might play a crucial role in ovarian cancer progression, adaptation and eventual resistance to chemotherapy through differential processing of CLU isoforms. Specifically, sCLU as an antiapoptotic protein, upregulated in an adaptive cell‐survival manner by chemotherapy, confers resistance to various cell‐death triggers. © 2009 UICC
The melanoma specific 9.2.27PE immunotoxin efficiently kills melanoma cells in vitro
Authors: Risberg Karianne , Fodstad Øystein , Andersson Yvonne
Published: February 2009

Malignant melanomas are generally drug resistant and have a very poor prognosis. We have studied the effects of a chemical conjugate of pseudomonas exotoxin A (PE) and the antibody 9.2.27, which recognizes the high molecular weight melanoma associated antigen (HMW‐MAA) expressed in most malignant melanomas and melanoma cell lines. We demonstrate that the 9.2.27PE immunotoxin (IT) induces cell death in malignant melanoma cells through protein synthesis inhibition followed by some morphological and biochemical features of apoptosis, like rounding up of cells, chromatin condensation and inactivation of PARP. Unlike previous results with the 425.3PE IT in breast cancer cells, we detected no depolarization of the mitochondrial membrane after 9.2.27PE IT treatment. This is likely due to the lack of strong activation of caspase‐8 and caspase‐3. The lack of depolarization suggests that cytochrome c, a molecule that triggers activation of caspase‐3, was retained within the mitochondria. In addition, the protein level of the antiapoptotic Bcl‐2 did not decrease in contrast to other antiapoptotic molecules belonging to the inhibitor of apoptosis and the Bcl‐2 family. This suggests that Bcl‐2 may play a role in maintaining the mitochondrial membrane integrity in the 9.2.27PE‐treated cells. Nevertheless, 9.2.27PE IT efficiently killed malignant melanoma cells that can be ascribed to inhibition of protein synthesis followed by some morphological and biochemical features of apoptosis. © 2009 UICC
International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons
Authors: Mirabello Lisa , Troisi Rebecca J. , Savage Sharon A.
Published: February 2009

Osteosarcoma incidence rates in the United States peak in adolescence and in the elderly. The international patterns of osteosarcoma incidence in children have been described, whereas those for young, middle age or elderly adults have not. Using the Cancer Incidence in Five Continents, International Agency for Cancer Research database we compared incidence rates for children and adolescents (age 0–24 years), the middle age group (25–59 years) and elderly (≥60 years) persons by world regions and individual countries. Overall, worldwide osteosarcoma incidence rates were quite similar in the younger age groups. The greatest variation in incidence rates was observed in the elderly. Published 2009 UICC
Ribosome‐inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase‐1 selectively in premalignant and malignant prostate cancer cells
Authors: Xiong Su Dao , Yu Kang , Liu Xin Hua , Yin Li Hui , Kirschenbaum Alexander , Yao Shen , Narla Goutham , DiFeo Analisa , Wu Jian Buo , Yuan Yong , Ho Shuk‐Mei , Lam Ying Wai , Levine Alice C.
Published: February 2009

Epidemiologic evidence suggests that a diet rich in fruits and vegetables is associated with a reduced risk of prostate cancer (PCa) development. Although several dietary compounds have been tested in preclinical PCa prevention models, no agents have been identified that either prevent the progression of premalignant lesions or treat advanced disease. Momordica charantia, known as bitter melon in English, is a plant that grows in tropical areas worldwide and is both eaten as a vegetable and used for medicinal purposes. We have isolated a protein, designated as MCP30, from bitter melon seeds. The purified fraction was verified by SDS‐PAGE and mass spectrometry to contain only 2 highly related single chain Type I ribosome‐inactivating proteins (RIPs), α‐momorcharin and β‐momorcharin. MCP30 induces apoptosis in PIN and PCa cell lines in vitro and suppresses PC‐3 growth in vivo with no effect on normal prostate cells. Mechanistically, MCP30 inhibits histone deacetylase‐1 (HDAC‐1) activity and promotes histone‐3 and ‐4 protein acetylation. Treatment with MCP30 induces PTEN expression in a prostatic intraepithelial neoplasia (PIN) and PCa cell lines resulting in inhibition of Akt phosphorylation. In addition, MCP30 inhibits Wnt signaling activity through reduction of nuclear accumulation of β‐catenin and decreased levels of c‐Myc and Cyclin‐D1. Our data indicate that MCP30 selectively induces PIN and PCa apoptosis and inhibits HDAC‐1 activity. These results suggest that Type I RIPs derived from plants are HDAC inhibitors that can be utilized in the prevention and treatment of prostate cancer. © 2009 UICC
Effects of dietary factors and the NAT2 acetylator status on gastric cancer in Koreans
Authors: Zhang Yan Wei , Eom Sang‐Yong , Kim Yong‐Dae , Song Young‐Jin , Yun Hyo‐Yung , Park Joo‐Seung , Youn Sei‐Jin , Kim Byung Sik , Kim Heon , Hein David W.
Published: February 2009

Environmental dietary carcinogens and genetic polymorphisms in metabolic enzymes have been reported to be the risk factors for gastric cancer. This study was undertaken to investigate the effects of the diet, the N‐acetyltransferase (NAT) 2 acetylation status and their interaction on gastric cancer risk. The study population consisted of 471 gastric cancer patients and 471 age‐ and sex‐matched control subjects. NAT2 genotypes were identified using single‐nucleotide primer extension reaction methods. Thirty‐one alleles related to 12 polymorphism sites were assayed in this study. Significantly increased odds ratios were observed in former smokers (OR = 2.39, 95% CI = 1.57–3.62), heavy drinkers (OR = 1.28, 95% CI = 1.06–1.55) and individuals who eat well‐done meat (OR = 1.24, 95% CI = 1.09–1.41). The odds ratios (95% CI) for high intake of kimchi, stews and soybean paste were 3.27 (2.44–4.37), 1.96 (1.50–2.58) and 1.63 (1.24–2.14), respectively. The NAT2 genotype alone was not associated with gastric cancer risk. A significant gene–environment interaction was observed between environmental carcinogens and NAT2 genotypes. The odds ratios for kimchi, stews and soybean paste were higher in slow/intermediate acetylators than in rapid acetylators. The odds ratios for slow/intermediate acetylators were 2.28 (95% CI: 1.29–4.04) for light smokers and 3.42 (95% CI: 2.06–5.68) for well‐done meat intake. The NAT2 acetylator genotype may be an important modifier of the effects of environmental factors on gastric cancer risk. © 2009 UICC
An orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in distant metastasis
Authors: Doll Andreas , Gonzalez Marta , Abal Miguel , Llaurado Marta , Rigau Marina , Colas Eva , Monge Marta , Xercavins Jordi , Capella Gabriel , Diaz Berta , Gil‐Moreno Antonio , Alameda Francesc , Reventos Jaume
Published: February 2009

Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries. Metastasis is the major cause of endometrial cancer deaths. Therefore, there is a vital need for clinically relevant in vivo models allowing the elucidation of the molecular and cellular mechanisms underlying metastatic behavior. In this study, we describe an innovative experimental orthotopic model of human endometrial carcinoma. Implantation in the bifurcation of the uterine horns resulted in tumors integrated into the myometrial compartment, which can be used and further exploited for the study of in vivo angiogenesis, myometrial invasion, and the metastatic capacity of endometrial cancer cells. This orthotopic model also represents a suitable tool to analyze how tumorigenesis and distant metastasis of endometrial cancer might be influenced by gene alteration, by modulating its expression in the original cancer cell line. One of the candidate genes implicated in endometrial cancer is the transcription factor RUNX1. The over‐expression of RUNX1 in the endometrial cancer cell line HEC1A and the transplantation of these cells to the uterus of nude mice were associated specifically with distant metastasis in the lung. RUNX1 plays a role in the establishment of metastases in endometrial cancer. Translated to the clinics, these models would be equivalent to an advanced undifferentiated carcinoma with node affectation (stage IIIC) and distant metastasis (stage IVB). These patients would be candidates for adjuvant therapy, not efficient until today, and therefore, our models are actually suitable for the design and evaluation of experimental therapies. © 2009 UICC
Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography
Authors: Jannasch Katharina , Dullin Christian , Heinlein Christina , Krepulat Frauke , Wegwitz Florian , Deppert Wolfgang , Alves Frauke
Published: February 2009

Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat‐panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene‐induced mammary carcinogenesis (WAP‐T mice). WAP‐T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3‐dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm3) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three‐dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP‐T mouse, and thereafter show divergent growth rates and distinct vascularization patterns. © 2009 UICC
The PTEN regulator DJ‐1 is associated with hTERT expression in clear cell renal cell carcinoma
Authors: Sitaram Raviprakash T. , Cairney Claire J. , Grabowski Pawel , Keith W. Nicol , Hallberg Bengt , Ljungberg Börje , Roos Göran
Published: February 2009

DJ‐1 is as a novel regulator of the tumor suppressor PTEN with stimulatory effects on PI3K‐AKT/PKB signaling, one possible target of which is cMyc. The catalytic unit of the telomerase complex, hTERT, can be activated at different levels, including transcriptionally by cMyc and through phosphorylation by AKT/PKB. The aim of the study was to analyze the putative signaling pathway encompassing DJ‐1, cMyc and hTERT in a series of 176 renal cell carcinomas (RCC) and experimentally in cell lines. DJ‐1 mRNA expression was significantly elevated in clear cell RCC (ccRCC) compared with in papillary RCC (pRCC; p = 0.005) and kidney cortex tissue (p < 0.001). ccRCC and pRCC demonstrated higher cMyc RNA levels than in kidney cortex (p < 0.001 for both) as well as increased levels of hTERT RNA (p < 0.001 and p = 0.011, respectively). DJ‐1 was positively correlated to cMyc and hTERT in ccRCC (p < 0.001 and p = 0.019, respectively), but not in pRCC, indicating that this pathway could have a functional significance in ccRCC. siRNA knock down of DJ‐1 induced downregulation of cMyc and hTERT mRNA associated with decreased expression of pAKT and cMyc protein levels. hTERT promoter activity was upregulated after DJ‐1 transfection and this upregulation was inhibited after mutation of the cMyc binding sites. These experimental data support the functional link among DJ‐1, cMyc and hTERT expression as indicated in the tumor material. Neither DJ‐1, cMyc nor hTERT mRNA levels were associated with proliferation (S‐phase fraction), telomere length or prognosis in ccRCC. © 2009 UICC
Biocompatibility and safety evaluation of a ricinoleic acid‐based poly(ester‐anhydride) copolymer after implantation in rats
Authors: Vaisman Boris , Motiei Menachem , Nyska Abraham , Domb Abraham J.
Published: February 2009

The aim of this study was to evaluate the safety and tissue compatibility of an injectable biodegradable poly(ester‐anhydride) copolymer of ricinoleic acid (RA) and sebacic acid (SA) in rats. The absorbable biomaterial containing 70% w/w of RA and 30% w/w of SA [P(SA‐RA) 3:7] was implanted in rats in two separate studies: (1) at high doses subcutaneously (SC) and intramuscularly (IM) simultaneously into the same animal and (2) intracranially (IC). The safety was established in the high‐dose administration experiment. No systemic tissue damage, polymer‐related lesions, or abnormalities could be detected in the animals. The histopathological evaluation of the SC and IM P(SA‐RA) 3:7 implanted sites suggested a typical foreign body reaction (FBR) to biomaterials, and was characterized by excellent tissue repair and good tissue tolerance. In the second experiment, no neurological deficits or behavior changes suggestive of systemic or localized toxicity were observed in the animals implanted IC with the polymer. Only minimal, well‐demarcated inflammatory response was observed on days 14 and 21 and consisted of glia cells. No abnormalities were noted in the brain tissue parenchyma located further from the edges of the implant. These results demonstrated that the P(SA‐RA) 3:7 copolymer was tolerated well by the animals and compatible with rat subcutaneous, muscle and brain tissues. The biodegradable polymeric system described here could be used as a scaffold for varied applications in localized and sustained delivery of therapeutic agents. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Initial osteoblast functions on Ti‐5Zr‐3Sn‐5Mo‐15Nb titanium alloy surfaces modified by microarc oxidation
Authors: Zhao Lingzhou , Wei Yanping , Li Jianxue , Han Yong , Ye Ruidong , Zhang Yumei
Published: February 2009

This study is intended to evaluate the effects of microarc oxidation (MAO) on the biocompatibility of near β titanium alloy Ti‐5Zr‐3Sn‐5Mo‐15Nb (TLM) in vitro. Two porous bioactive surfaces with different surface characteristics were grown on TLM substrates via MAO process at two different final voltages. Both calcium and phosphorus were incorporated into the oxidized surfaces, and their content was dependent on the voltage applied. Surface roughness was enhanced on the MAO surfaces, which was higher when a higher voltage was applied. After MAO treatment, water contact angles became smaller and surface energies were increased, especially the polar components, which were also related to the MAO final voltage. Cell culture experiments showed an enhanced osteoblasts adhesion, spread, and viability on the microarc oxidized surfaces, and better cell spread and viability were found on the surface formed at 450 V than that at 300 V. No obvious variations in gene expression of integrin β1 (Itgβ1), core binding factor‐α1, osteopontin, collagen type I α2‐chain, and fibronectin by osteoblasts were observed on different surfaces. The expression of osteocalcin was strikingly increased on MAO surfaces after 72 h, thus indicating enhanced osteoblasts differentiation on MAO surfaces. Interestingly, obvious enhanced bone morphogenetic proteins (BMP)‐2 and BMP‐4 expression was observed on MAO surfaces, which may be a reason for the enhanced osteoblasts functions on MAO‐modified TLM surfaces. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
A new route to produce starch‐based fiber mesh scaffolds by wet spinning and subsequent surface modification as a way to improve cell attachment and proliferation
Authors: Tuzlakoglu K. , Pashkuleva I. , Rodrigues M. T. , Gomes M. E. , van Lenthe G. H. , Müller R. , Reis R. L.
Published: February 2009

This study proposes a new route for producing fiber mesh scaffolds from a starch–polycaprolactone (SPCL) blend. It was demonstrated that the scaffolds with 77% porosity could be obtained by a simple wet‐spinning technique based on solution/precipitation of a polymeric blend. To enhance the cell attachment and proliferation, Ar plasma treatment was applied to the scaffolds. It was observed that the surface morphology and chemical composition were significantly changed because of the etching and functionalization of the fiber surfaces. XPS analyses showed an increase of the oxygen content of the fiber surfaces after plasma treatment (untreated scaffolds O/C:0.32 and plasma‐treated scaffolds O/C:0.41). Both untreated and treated scaffolds were examined using a SaOs‐2 human osteoblast‐like cell line during 2 weeks of culture. The cell seeded on wet‐spun SPCL fiber mesh scaffolds showed high viability and alkaline phosphatase enzyme activity, with those values being even higher for the cells seeded on the plasma‐treated scaffolds. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Preparation and characterization of polyethylenimine‐coated Fe3O4‐MCM‐48 nanocomposite particles as a novel agent for magnet‐assisted transfection
Authors: Yiu Humphrey H. P. , McBain Stuart C. , Lethbridge Zoe A. D. , Lees Martin R. , Dobson Jon
Published: February 2009

A new type of magnetic nanoparticle was synthesized using mesoporous silica MCM‐48 as a template. Magnetite (Fe3O4) nanocrystals were incorporated onto the MCM‐48 silica structure by thermal decomposition of iron(III) acetylacetonate. The particle size of these Fe3O4‐MCM‐48 composite particles is around 300 nm with an iron oxide content of ca. 20% w/w. Measurements from SQUID magnetometry suggest that these nanoparticles possess superparamagnetic properties similar to those of Fe3O4 nanoparticles. By coating positively charged polyethylenimine on to the surface, DNA can be bound onto the Fe3O4‐MCM‐48 nanoparticles. Transfection studies showed that these PEI‐Fe3O4‐MCM‐48 particles were highly effective as a transfection reagent, and a 400% increase of transfection efficiency compared with the commercial products was recorded. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Intradiscal drug delivery system for the treatment of low back pain
Authors: Lee Jin Whan , Lim Tae‐Hong , Park Joon B.
Published: February 2009

Possible solution to the long‐term control of the low back pain (LBP) would be by using an injectable pain drug carrier that can be delivered locally. The drug can be released in a controlled manner. It is also allowed to inject repeatedly more drugs percutaneously with a minimal invasion. The main objective of this study was to develop such a drug delivery system (DDS) for long‐term control of discogenic LBP. The DDS consists of in situ forming hydrogel matrix (Pluronic F127® plus sodium hyaluronate) containing microspheres (MS). The solid MS were used for long‐term release of the drugs. Both hydrogel matrix and MS contained a model drug, bupivacaine base (BB). The phase transition (liquid at room temperature, gel at around body temperature) could be manipulated by changing the composition of the hydrogel. In vitro test showed that ∼3% (w/w) of the BB loaded to MS were released during 42 days, demonstrating a good potential for sustained release of bupivacaine. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Synthesis of four racemic nicotine isotopomers doubly labelled with stable isotope
Authors: Hatton Wilfried , Silvestre Virginie , Robins Richard J. , Mathé‐Allainmat Monique , Lebreton Jacques
Published: February 2009

Four racemic nicotine isotopomers, doubly labelled with stable isotope, were prepared for use in studies of plant metabolism. First, starting from halogeno nicotinates, one deuterium was introduced into the pyridine moiety by reductive dehalogenation with zinc, and choosing deuterated acetic acid as the acidic medium. Pyridine2H‐labelled nornicotine derivatives were then formed in two reaction steps, a condensation reaction withN‐vinylpyrrolidinone followed by catalytic hydrogenation. The deuteromethylation of these monodeuterated nornicotines was achieved by reduction of the corresponding ethyl carbamates with deuterated lithium aluminium hydride. The four regioisotopomers obtained were at the least 90% labelled on each site, sufficient for the metabolic studies envisaged. Copyright © 2009 John Wiley & Sons, Ltd.
Climate variability and change in the Greater Alpine Region over the last two centuries based on multi‐variable analysis
Authors: Brunetti Michele , Lentini Gianluca , Maugeri Maurizio , Nanni Teresa , Auer Ingeborg , Böhm Reinhard , Schöner Wolfgang
Published: February 2009

An extensive analysis of the HISTALP database is presented with the aim of giving a comprehensive picture of secular climate variability and change in the Greater Alpine Region (GAR, 4–19 E, 43–49 N). The HISTALP database encompasses 242 sites and concerns temperature, pressure, precipitation, cloudiness, sunshine duration, vapour pressure and relative humidity. The analyses are based on four regional mean records representing different GAR low‐level areas and on an additional mean record representing high‐level locations.

The first goal of the paper is to give an overview of the seasonal and annual records for the different variables, aiming to highlight both variability on decadal time scale and long‐term evolution. Then it focuses on trend and correlation analysis. Trends are presented both for the period of common data availability for all regional average series and for moving windows that permit studying the trends over a wide range of timescales. Correlations among the different variables are presented both for the regional average series and for their high‐pass‐filtered versions.

The analyses, beside highlighting a warming that is about twice as large as the global trend, also show that the different variables have responded in different ways to this warming and that the mutual interactions linking the different variables are often present only at specific temporal scales and only in parts of the GAR and in defined seasons. In spite of this complex behaviour, which may also be due to some residual inhomogeneities still affecting the data, the analyses give evidence that the HISTALP database has an excellent internal consistency and show that the availability of a multi‐variable database turns out to be very useful in order to evaluate the reliability of the reconstruction of each variable and to better understand the behaviour and the mutual interactions of the different variables. Copyright © 2009 Royal Meteorological Society
A Raman spectroscopic study of the uranyl mineral rutherfordine—revisited
Authors: Frost Ray L. , Čejka Jiří
Published: February 2009

The molecular structure of the uranyl mineral rutherfordine has been investigated by the measurement of the near‐infrared (NIR) and Raman spectra and complemented with infrared spectra including their interpretation. The spectra of rutherfordine show the presence of both water and hydroxyl units in the structure as evidenced by IR bands at 3562 and 3465 cm−1 (OH) and 3343, 3185 and 2980 cm−1 (H2O). Raman spectra show the presence of four sharp bands at 3511, 3460, 3329 and 3151 cm−1. Corresponding molecular water bending vibrations were only observed in both Raman and infrared spectra of one of two studied rutherfordine samples. The second rutherfordine sample studied contained only hydroxyl ions in the equatorial uranyl plane and did not contain any molecular water. The infrared spectra of the (CO3)2− units in the antisymmetric stretching region show complexity with three sets of carbonate bands observed. This combined with the observation of multiple bands in the (CO3)2− bending region in both the Raman and IR spectra suggests that both monodentate and bidentate (CO3)2− units may be present in the structure. This cannot be exactly proved and inferred from the spectra; however, it is in accordance with the X‐ray crystallographic studies. Complexity is also observed in the IR spectra of (UO2)2+ antisymmetric stretching region and is attributed to non‐identical UO bonds. UO bond lengths were calculated using wavenumbers of the ν3 and ν1 (UO2)2+ and compared with data from X‐ray single crystal structure analysis of rutherfordine. Existence of solid solution having a general formula (UO2)(CO3)1−x(OH)2x.yH2O (x, y ≥ 0) is supported in the crystal structure of rutherfordine samples studied. Copyright © 2009 John Wiley & Sons, Ltd.
Raman spectroscopic study of the mixed anion mineral yecoraite Bi5Fe3O9(Te4+O3)(Te6+O4)2·9H2O
Authors: Frost Ray L. , Keeffe Eloise C.
Published: February 2009

Tellurates are rare minerals as the tellurate anion is readily reduced to the tellurite ion. Often minerals with both tellurate and tellurite anions are found. An example of such a mineral containing tellurate and tellurite is yecoraite. Raman spectroscopy has been used to study this mineral, the exact structure of which is unknown. Two Raman bands at 796 and 808 cm−1 are assigned to the ν1(TeO4)2− symmetric and ν3(TeO3)2− antisymmetric stretching modes and Raman bands at 699 cm−1 are attributed to the ν3(TeO4)2− antisymmetric stretching mode and the band at 690 cm−1 to the ν1(TeO3)2− symmetric stretching mode. The intense band at 465 cm−1 with a shoulder at 470 cm−1 is assigned the (TeO4)2− and (TeO3)2− bending modes. Prominent Raman bands are observed at 2878, 2936, 3180 and 3400 cm−1. The band at 3936 cm−1 appears quite distinct and the observation of multiple bands indicates the water molecules in the yecoraite structure are not equivalent. The values for the OH stretching vibrations listed provide hydrogen bond distances of 2.625 Å (2878 cm−1), 2.636 Å (2936 cm−1), 2.697 Å (3180 cm−1) and 2.798 Å (3400 cm−1). This range of hydrogen bonding contributes to the stability of the mineral. A comparison of the Raman spectra of yecoraite with that of tellurate containing minerals kuranakhite, tlapallite and xocomecatlite is made. Copyright © 2009 John Wiley & Sons, Ltd.
Vibrational modes of rare‐earth formates
Authors: Silva E. N. , Moura M. R. , Ayala A. P. , Guedes I. , Polla G. , Vega D. R. , Tobia D. , Saleta M. E.
Published: February 2009

In this work we investigate the room‐temperature Raman spectra of several rare‐earth [RE(HCOO)3; RE = La, Pr, Nd, Gd, Tb and Y] formates. Polarized measurements were carried out for La(HCOO)3 yielding the observation of most of the Raman‐active phonons predicted by group theory analysis. The respective assignment is given based on the formate vibrations and correlations with previous results in other RE(HCOO)3 systems. The wavenumber ‘softening’ observed when RE goes from Y to La is accounted for the lattice expansion. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis and Characterization of Large‐Core Star Polymers and Polymer Networks: Effects of Arm Length and Composition of the Cross‐Linking Mixture
Authors: Kafouris Demetris , Gradzielski Michael , Patrickios Costas S.
Published: February 2009

Large‐core star polymers (LCSPs) and polymer networks were prepared using sequential group transfer polymerization (GTP) for the synthesis of linear poly(methyl methacrylate) (polyMMA) arms, followed by their cross‐linking using a mixture of MMA monomer and ethylene glycol dimethacrylate (EGDMA) cross‐linker. High monomer/cross‐linker molar ratios and short arms favored the formation of polymer networks, whereas the opposite conditions favored the formation of LCSPs. LCSPs presented two populations: star polymers and covalently linked star polymer aggregates. The size of the non‐aggregated star polymers, and the size and fraction of the star polymer aggregates passed through a maximum as the amount of the monomer in the cross‐linking mixture increased. The degrees of swelling in tetrahydrofuran (THF) of the networks, the sol fraction extracted from them, and the percentage of linear polymer in the sol fraction increased as the degree of polymerization of the arms increased.

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