bluuebunny/crossref_metadata_2025 huggingface dataset:
Wnt2 as a new therapeutic target in malignant pleural mesothelioma
Authors: Mazieres Julien , You Liang , He Biao , Xu Zhidong , Twogood Sarah , Lee Amie Y. , Reguart Noemi , Batra Sonny , Mikami Iwao , Jablons David M.
Published: May 2005

Malignant mesothelioma of the pleura (MPM) is a highly aggressive neoplasm with a poor prognosis and limited treatment options. A better understanding of its pathogenesis is essential to developing alternative therapeutic strategies. We previously demonstrated that the Wnt signaling pathway is activated in MPM through the overexpression of disheveled proteins. To extend our knowledge of Wnt signaling activation in MPM, we performed Wnt‐specific microarrays in normal pleura and MPM. We found that the most common event in MPM was the upregulation of Wnt2. We inhibited Wnt2 by siRNA and a monoclonal anti‐Wnt2 antibody and analyzed their effects on apoptosis and downstream signaling effectors. We then assessed the antiproliferative effects of the Wnt2 antibody and Alimta, one of the current standard treatments of MPM. We confirmed Wnt2 overexpression at the mRNA and protein level in MPM cell lines and tissues. We then demonstrated that inhibition of Wnt2 by siRNA or a monoclonal antibody induces programmed cell death in MPM cells. We next analyzed the effects of the anti‐Wnt2 antibody and of Alimta on MPM cell proliferation. We found that although Wnt2 antibody by itself had less antiproliferative potency than Alimta, the two in combination had substantially more activity than Alimta alone. We thus propose that inhibition of Wnt2 is of therapeutic interest in the development of more effective treatments for MPM. © 2005 Wiley‐Liss, Inc.
Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib
Authors: Bauer Sebastian , Hartmann Jörg Thomas , de Wit Maike , Lang Hauke , Grabellus Florian , Antoch Gerald , Niebel Wolfgang , Erhard Jochen , Ebeling Peter , Zeth Matthias , Taeger Georg , Seeber Siegfried , Flasshove Michael , Schütte Jochen
Published: May 2005

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Long‐term survival of patients with metastatic disease has only been observed in patients with completely resected disease. Recently, the tyrosine kinase inhibitor imatinib has been found to yield responses in the majority of patients with metastatic GIST suggesting improved resectability in responding patients. Combined treatment approaches including resective surgery after imatinib treatment in patients with advanced metastatic disease have rarely been explored. We report a series of 90 patients with metastatic GIST in whom treatment with imatinib enabled 12 patients with mostly recurrent and extensive disease to be considered for resection of residual disease. In 11 of these patients, complete resection could be achieved. Viable tumor cells were found in all but one resected specimens suggesting that despite favorable radiological or clinical responses, imatinib is unlikely to induce pathological complete responses. Until more mature data from prospective trials are available, these data suggest that an early aggressive surgical approach should be considered for all patients with metastatic GIST. Further trials investigating a combined surgical and pre/postoperative treatment with imatinib in patients with advanced metastatic GIST are warranted. © 2005 Wiley‐Liss, Inc.
Mantle cell lymphomas with low levels of cyclin D1 long mRNA transcripts are highly proliferative and can be discriminated by elevated cyclin A2 and cyclin B1
Authors: Sander Birgitta , Flygare Jenny , Porwit‐MacDonald Anna , Smith C.I. Edvard , Emanuelsson Emma , Kimby Eva , Liden Johan , Christensson Birger
Published: May 2005

The role of transcript variants of cyclin D1 in cancer biology is unclear. Most tumors with high levels of cyclin D1 express 2 transcripts due to alternative splicing: one full‐length transcript of 4.4 kb and one short transcript of approximately 1.7 kb. The short transcript lacks part of the 3′UTR region regulating mRNA stability and has a longer half‐life. In our study, the contribution of each of these mRNAs to gene expression and cell proliferation has been investigated in mantle cell lymphoma (MCL), a B cell lymphoma characterized by a specific gene translocation resulting in enhanced expression of cyclin D1. A subset of MCL tumors with low levels of the long cyclin D1 transcript (cyclin D1 3′UTR) was identified by quantitative PCR and by oligonucleotide array hybridization. This tumor‐subset had 3.4‐fold higher levels of the short form of cyclin D1 mRNA (p < 0.0001) and had higher expression of cyclin D1 protein. Gene expression analysis identified a number of cell‐cycle regulatory genes as upregulated. There was a significant difference in frequencies of cyclin B1 (p = 0.0006) and cyclin A2 (p = 0.0006) positive cells that discriminated MCL with low cyclin D1 3′UTR from other highly proliferative MCL. Among differentially expressed genes, there was a highly upregulated gene with homology to the group of cell‐cycle promoting E2F transcription partners, E2F_TDP5. Several of the upregulated genes, such as TOP2A, AURORA A and RRM2 may influence a response to therapy. Identification of MCL with low cyclin D1 3′UTR is important because it seems to be associated with shorter overall survival. © 2005 Wiley‐Liss, Inc.
Gastrointestinal stromal tumors in Iceland, 1990–2003: The Icelandic GIST study, a population‐based incidence and pathologic risk stratification study
Authors: Tryggvason Geir , Gíslason Hjörtur G. , Magnússon Magnús K. , Jónasson Jón G.
Published: May 2005

Gastrointestinal stromal tumor (GIST) is a newly defined clinical and pathologic entity. This study examines the whole population‐based incidence of GIST as well as pathologic risk stratification schemes. All patients diagnosed in Iceland with a gastrointestinal mesenchymal tumor over the years 1990–2003 were evaluated with an immunohistochemical panel including staining for c‐kit. The age‐adjusted incidence of GIST was calculated. Size, mitotic rate per 50 HPF and various other pathologic parameters were evaluated. Each tumor was categorized into 1 of 4 recently defined NIH risk stratification categories. Fifty‐seven of the mesenechymal gastrointestinal tumors were positive for c‐kit and therefore categorized as GIST. The annual incidence for the study period is 1.1 per 100,000. The median age of patients was 65.8 years and median tumor size was 4.6 cm. Only 2 of 35 gastric tumors fall into the NIH high‐risk category while half of the nongastric tumors (11 of 22) fall into this high‐risk category. Eight of the 57 tumors (14%) metastasized, 7 of which were nongastric. The positive predictive value for malignant behavior of the high‐risk category is 46%. The negative predictive value of low‐ and very‐low‐risk NIH category is 100%. Pathologic predictors of malignant behavior are tumor size, mitotic rate, mucosal disruption, necrosis and high cellularity. Nongastric GISTs are clearly at much higher risk of a malignant behavior than gastric GISTs. This population‐based GIST study estimates the incidence of GISTs at 1.1 per 100,000 and furthermore supports the NIH consensus categories for the prediction of malignant behavior of GISTs. © 2005 Wiley‐Liss, Inc.
Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer
Authors: Weikert Steffen , Krause Hans , Wolff Ingmar , Christoph Frank , Schrader Mark , Emrich Thomas , Miller Kurt , Müller Markus
Published: May 2005

The aim of our study was to prospectively evaluate the potential diagnostic value and clinical applicability of quantitative analysis of telomerase subunits gene expression in urine for noninvasive detection of bladder cancer. Expression levels of human telomerase reverse transcriptase (hTERT) and human telomerase RNA (hTR) were analyzed by real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) in urine samples from 163 subjects with bladder cancer and 237 controls (163 individuals with benign genitourinary diseases; 74 healthy subjects). The sensitivity, specificity and optimal cutoffs were determined and compared to the corresponding values obtained by voided urine cytology. Quantitative urinary hTR analysis detects bladder cancer with an overall sensitivity of 77.0%, whereas hTERT analysis reached a sensitivity of 55.2%. The majority of undetected tumors were small, low‐grade pTa lesions. Both hTR and hTERT proved to be significantly more sensitive than cytology (34.5%; p < 0.001). Specificities for hTR, hTERT and cytology were 72.1%, 85.0% and 92.7%, respectively, in the total study population and 96.9%, 89.2% and 100%, respectively, in healthy subjects. Higher diagnostic accuracy was achieved by hTR than by hTERT analysis (p < 0.05). The specificity of hTR increased to 85.0% in the total population if urinary leukocyte contamination was excluded. These data suggest that quantitative hTR analysis is the most accurate telomerase‐based test for bladder cancer detection and has the potential to replace cytology as a noninvasive biomarker for disease diagnosis and follow‐up. © 2005 Wiley‐Liss, Inc.
Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer
Authors: Oki Eiji , Baba Hideo , Tokunaga Eriko , Nakamura Toshihiko , Ueda Naoyuki , Futatsugi Motonori , Mashino Kohjiro , Yamamoto Manabu , Ikebe Masahiko , Kakeji Yoshihiro , Maehara Yoshihiko
Published: May 2005

Growth factor receptor‐mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells. We describe a pathway that involves AKT/PI3K to mediate chemoresistance in gastric cancer patients. Primary gastric carcinoma tissues and corresponding normal mucosa were obtained from 76 gastric cancer patients who underwent surgery in the Department of Surgery II in Kyushu University Hospital from the years 1996–2000. AKT activation was investigated by immunostaining with a phosphorylation‐specific antibody, and LOH (loss of heterozygosity) of PTEN was studied in the same samples. AKT was phosphorylated in 22 cases (28.9%) of gastric cancer cases. AKT and phosphorylated AKT were not correlated with any clinicopathological factor. We found that the gastric cancer patients who had higher AKT phosphorylation (activated AKT) seemed to have LOH of PTEN (p = 0.0008). When the chemotherapeutic sensibilities of these patients were studied in an MTT assay, it was found that the activated AKT was associated with increased resistance to multiple chemotherapeutic agents (5‐fluorouracil, adriamycin, mitomycin C and cis‐platinum). The results of our study indicate that AKT activation and LOH of PTEN plays an important role in conferring a broad‐spectrum chemoresistance in gastric cancer patients. It also indicates that AKT may therefore be a novel molecular target for therapies or chemosensitivity tests that improve the outcomes of gastric cancer patients. © 2005 Wiley‐Liss, Inc.
Vitamin E amides, a new class of vitamin E analogues with enhanced proapoptotic activity
Authors: Tomic‐Vatic Adisa , EyTina John , Chapman James , Mahdavian Elahe , Neuzil Jiri , Salvatore Brian A.
Published: May 2005

Vitamin E (VE) analogues, epitomized by α‐tocopheryl succinate (α‐TOS), are proapoptotic agents with selective antineoplastic activity. The molecule of α‐TOS comprises several structurally and functionally distinct moieties that can be modified in order to yield analogues with higher activity. In order to find analogues with higher apoptogenic efficacy, we prepared novel compounds where the ester bond was replaced by an amide bond. All of these analogues were significantly more proapoptotic than their ester counterparts, with α‐tocopheryl maleyl amide being the most effective. Importantly, methylation of the free carboxylic group completely obliterated apoptogenic activity of the compounds. Similarly as shown for the ester analogues, the amides induced apoptosis by mitochondrial destabilization. Superiority of amides over the ester analogues may be due to their higher partitioning into the lipid phase, as suggested by the log p‐values that were lower for the amides than the corresponding esters. In conclusion, we present evidence that modification of the ester bond of agents such as α‐TOS can be used as a basis for generating novel analogues with higher efficacy of killing malignant cells, an activity that suggests anticancer effect of the agents. © 2005 Wiley‐Liss, Inc.
Differential expression of steroid receptors in prostate tissues before and after radiation therapy for prostatic adenocarcinoma
Authors: Torlakovic Emina , Lilleby Wolfgang , Berner Aasmund , Torlakovic Goran , Chibbar Rajni , Furre Torbjørn , Fosså Sophie D.
Published: May 2005

The expression, distribution and the role of steroid receptors in benign and malignant untreated prostate tissues is well recognized, however, the status of steroid receptors in prostate after radiotherapy (RT) for adenocarcinoma has not yet been studied fully. Immunohistochemical evaluation of androgen receptor (AR), estrogen receptor‐alpha (ER‐α), estrogen receptor‐beta (ER‐β), and progesterone receptor (PR) was carried out in prostate needle biopsies obtained before and after radiotherapy from 60 patients with adenocarcinoma. The ER‐β transcripts were also studied by RT‐PCR in LNCaP prostate carcinoma cell line before and 24 hr after γ‐irradiation at 0.5 Gy and 8.0 Gy. Significantly higher level of ER‐β expression was found in post‐radiation samples of prostate adenocarcinoma and benign epithelium. After RT, all steroid receptors were upregulated in prostatic stroma. Tumor AR expression did not change significantly. Although a positive association between AR and ER‐β expression was observed in pre‐treatment prostate adenocarcinoma, it was lost after RT suggesting that these 2 steroid receptors respond differently to RT. High levels of pretreatment tumor ER‐β were associated with local recurrence after RT and decreased biochemical recurrence‐free survival (p = 0.028). LNCaP cell line that expressed no ER‐β mRNA before γ‐irradiation, clearly expressed ER‐β mRNA 24 hr after 0.5 Gy and 8.0 Gy. Upregulation of all steroid receptors in the prostate stroma and upregulation of ER‐β in the tumor epithelium after RT, may represent a protective tissue response to radiation‐induced tissue injury. Although stromal AR was doubled after RT, the tumor and benign epithelium expression of AR seemed resistant to change by RT. © 2005 Wiley‐Liss, Inc.
Chromosome 1q loss of heterozygosity frequently occurs in sporadic insulinomas and is associated with tumor malignancy
Authors: Yang Ying‐Mai , Liu Tong‐Hua , Chen Yuan‐Jia , Jiang Wei‐Jun , Qian Jia‐Ming , Lu Xin , Gao Jie , Wu Sha‐Fei , Sang Xin‐Ting , Chen Jie
Published: May 2005

The pathogenesis of sporadic insulinomas is not clear, and there are no reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor. It was reported that 1q LOH might contribute to pathogenesis in gastrinomas and was correlated with tumor progression. However, little data are available on 1q LOH in sporadic insulinomas. In our study, we determine whether 1q LOH occurs in sporadic insulinomas and is associated with tumor malignancy by performing 1q allelotyping with 17 markers in 40 tumors and pair normal DNA. Thirty‐five (88%) insulinomas had 1q LOH. Of the 35 insulinomas with 1q LOH, 14 (40%) had 1q21.3‐23.2 LOH over a 7.5 cM region (SRO‐1), whereas LOH in 21 tumors (60%) occurred at 1q31.3 over an 11.4 cM area (SRO‐2). Of 24 tumors without MEN1 LOH, 20 had either SRO‐1 or SRO‐2 LOH (83%), whereas in 16 tumors with MEN1 LOH, 9 were shown to have LOH at either SRO‐1 or SRO‐2 (56%) (p = 0.065). This result suggests that LOH at 2 SRO might be MEN1 gene independent and may contribute to the pathogenesis in a subset of insulinomas without MEN1 gene LOH. The presence of 1q21.3‐23.2 LOH is significantly associated with malignancy of insulinomas (p = 0.014). The high frequency of LOH at 1q 21.3‐23.2 and 1q31.3 suggests these 2 areas may harbor putative tumor suppressor genes that may play an important role in the tumorigenesis of a subset of insulinomas. LOH at 1q21.3‐23.2, which was associated with tumor malignancy, could be one of the genetic markers for identifying malignancy in sporadic insulinomas. © 2005 Wiley‐Liss, Inc.
Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene
Authors: Hughes David J. , Ginolhac Sophie M. , Coupier Isabelle , Barjhoux Laure , Gaborieau Valérie , Bressac‐de‐Paillerets Brigitte , Chompret Agnès , Bignon Yves‐Jean , Uhrhammer Nancy , Lasset Christine , Giraud Sophie , Sobol Hagay , Hardouin Agnès , Berthet Pascaline , Peyrat Jean‐Philippe , Fournier Joelle , Nogues Catherine , Lidereau Rosette , Muller Danièle , Fricker Jean‐Pierre , Longy Michel , Toulas Christine , Guimbaud Rosine , Yannoukakos Drakoulis , Mazoyer Sylvie , Lynch Henry T. , Lenoir Gilbert M. , Goldgar David E. , Stoppa‐Lyonnet Dominique , Sinilnikova Olga M.
Published: May 2005

Marked variation in phenotypic expression among BRCA1 and BRCA2 mutation carriers may be partly explained by modifier genes that influence mutation penetrance. Variation in CAG/CAA repeat lengths coding for stretches of glutamines in the C‐terminus of the AIB1 protein (amplified in breast cancer 1, a steroid receptor coactivator) has been proposed to modify the breast cancer risk in women carrying germline BRCA1 mutations. We genotyped the AIB1 repeat length polymorphism from the genomic DNA of a group of 851 BRCA1 and 324 BRCA2 female germline mutation carriers to estimate an association with breast cancer risk modification. Hazard ratios (HR) were calculated using a Cox proportional hazards model. For BRCA1 and BRCA2 mutation carriers, analyzed separately and together, we found that women who carried alleles with 28 or more polyglutamine repeats had no increased risk of breast cancer compared to those who carried alleles with fewer repeats (HR for BRCA1/2 carriers = 0.88, 95% CI [confidence interval] = 0.75–1.04). Analyzing average repeat lengths as a continuous variable showed no excess risk of breast cancer (BC) in BRCA1 or BRCA2 mutation carriers (HR for average repeat length in BRCA1/2 carriers = 1.01, 95% CI = 0.92–1.11). These results strongly suggest that contrary to previous studies, there is no significant effect of AIB1 genetic variation on BC risk in BRCA1 mutation carriers and provide an indication that there is also no strong risk modification in BRCA2 carriers. © 2005 Wiley‐Liss, Inc.
Maternal height, pregnancy estriol and birth weight in reference to breast cancer risk in Boston and Shanghai
Authors: Lagiou Pagona , Samoli Evi , Lagiou Areti , Hsieh Chung‐Cheng , Adami Hans‐Olov , Trichopoulos Dimitrios
Published: May 2005

Birth weight has been positively associated with breast cancer risk in adult life and is positively associated with the principal pregnancy estrogen estriol. Birth weight is lower among Chinese women than among Caucasian women, but paradoxically, pregnancy estriol levels are higher among the former than the latter. We studied a cohort of 317 Caucasian pregnant women in Boston, MA, and 339 Chinese pregnant women in Shanghai, China. We investigated whether maternal height, which is inversely associated with pregnancy estriol levels, interacts with this hormone in relation to birth weight, thus accommodating the apparently contradictory ecologic and analytic evidence concerning the role of pregnancy estrogens on breast cancer risk in the offspring. In both Boston and Shanghai, there was a positive association of pregnancy estriol with birth weight among taller women, whereas among shorter women the association was essentially null. The relevant interaction terms were highly significant in Boston (p ≈ 0.006), whereas in Shanghai, where pregnant women were generally shorter, the interaction term was suggestive (p ≈ 0.14). We conclude that maternal height should be considered an important risk factor for breast cancer in the offspring since it is a crucial determinant of birth weight, both directly and through positive interaction with the principal pregnancy estrogen estriol. © 2005 Wiley‐Liss, Inc.
In vivo and in vitro characterization of human fibroblasts recruited selectively into human cancer stroma
Authors: Ishii Genichiro , Sangai Takafumi , Ito Takashi , Hasebe Takahiro , Endoh Yasushi , Sasaki Hiroki , Harigaya Kenichi , Ochiai Atsushi
Published: May 2005

Fibroblasts, which are a major component of cancer‐induced stroma, can have a significant impact on the progression of adjacent malignant epithelia. To characterize fibroblasts recruited into cancer‐induced stroma, we examined the recruitment efficiency of 9 human fibroblast cell lines into experimental tumors generated in immunodeficient mice. Green fluorescence protein (GFP)–labeled fibroblast cell lines and human pancreatic cancer cell line Capan‐1 were injected i.p. at different sites; the GFP‐labeled cells within xenografts were then analyzed. KM104GFP (bone marrow) and VA‐13GFP (lung) were selectively recruited into cancer stroma more efficiently than the other cell lines. KM104GFP cells did not affect tumor volume; however, VA‐13GFP cells increased tumor volume by about 2‐fold. After 5 cyclic in vivo passages of KM104GFP in Capan‐1, we selected a subpopulation with an 8.4‐fold higher recruitment efficiency (KM104GFP‐5G) compared to parental KM104GFP. KM104GFP‐5G also exhibited higher chemotaxis and chemoinvasion activity compared to KM104GFP in response to cancer‐released chemoattractant(s). Oligonucleotide microarray analysis identified 8 genes with >3‐fold upregulation and 6 genes with >3‐fold downregulation in KM104GFP‐5G. Immunohistochemistry confirmed that fibroblasts recruited into pancreatic cancer stroma strongly expressed carbonic anhydrase IX and keratin‐8, whose transcripts were upregulated in KM104GFP‐5G by oligonucleotide microarray analysis, whereas their expression in fibroblasts within noncancerous pancreatic stroma were under the detection level. Our results indicate that fibroblast recruitment is not selective with respect to organ origin and that particular fibroblast subpopulations with specific phenotypic characteristics could be recruited efficiently into cancer‐induced stroma. © 2005 Wiley‐Liss, Inc.
Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma
Authors: Oehlrich Nicole , Devitt Gerard , Linnebacher Michael , Schwitalle Yvette , Groβkinski Sonja , Stevanovic Stefan , Zöller Margot
Published: May 2005

Renal cell carcinomas (RCCs) are supposed to be immunogenic, and several clinical trials of immunotherapy using tumor lysate‐pulsed dendritic cells (DCs) have been performed. We report on the generation of RAGE‐1 and MAGE‐9 peptide‐specific CTL lines. RAGE‐1 and MAGE‐9 are expressed in 56% and 38% of RCCs. Seven MAGE‐9‐ and 13 RAGE‐1‐derived peptides were found to be immunogenic in the context of the HLA‐A*0201 MHC. CTLs were generated by coculture with peptide‐pulsed, activated B cells, which were easily generated in great quantities and displayed functional activity for a prolonged period of time. MAGE‐9 and RAGE‐1 peptide‐specific CTL lines were strictly peptide‐specific and displayed high cytotoxic activity not only against peptide‐loaded T2 cells but also against HLA‐A*0201‐positive RCC lines, which naturally express MAGE‐9, RAGE‐1 or both. Thus, B cells are well suited as APCs for the generation of large numbers of tumor peptide‐specific CTLs for adoptive transfer. MAGE‐9 as well as RAGE‐1 may well provide suitable targets for immunotherapy of RCC. © 2005 Wiley‐Liss, Inc.
Prevalence of types 16 and 33 is increased in high‐risk human papillomavirus positive women with cervical intraepithelial neoplasia grade 2 or worse
Authors: Bulkmans Nicole W.J. , Bleeker Maaike C.G. , Berkhof Johannes , Voorhorst Feja J. , Snijders Peter J.F. , Meijer Chris J.L.M.
Published: May 2005

High‐risk human papillomavirus (hrHPV) types are causally related to cervical cancer and its high‐grade precursor lesions. The risk posed by the different hrHPV types for the development of cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) needs to be established. Here, we present the hrHPV type‐distribution in relation to cytology and histology for women participating in a cervical screening program. From 44,102 women who participated in a population‐based cervical screening program in the Netherlands, 2,154 hrHPV GP5+/6+ PCR positive women were recruited to determine the distribution of 14 hrHPV types by reverse line blotting of GP5+/6+ PCR products. For each HPV type, associations with cytology and histologically confirmed ≥CIN2 were measured by odds ratios. HPV types 16 and 33 were more prevalent in women, amongst those containing a single hrHPV type, with moderate dyskaryosis or worse (>BMD) than in women with normal cytology, but only in case of underlying ≥CIN2 (OR 4.10, 95%CI 2.98–5.64 and OR 2.68, 95%CI 1.39–5.15, respectively). Similar results were obtained for women with double infections (OR 3.29, 95% CI 1.61–6.75 and OR 4.37, 95% CI 1.17–16.34). Coexisting types did not influence the prevalence of ≥CIN2 in HPV 16 or 33 positive women. The increased prevalence of type 16 and 33 in hrHPV positive women with ≥CIN2, compared to women with normal cytology, suggests that infection with these types confers an increased risk for development of ≥CIN2. Distinguishing these types may therefore have implications for future cervical screening strategies. © 2005 Wiley‐Liss, Inc.
Black–Scholes versus artificial neural networks in pricing FTSE 100 options
Authors: Bennell Julia , Sutcliffe Charles
Published: May 2005

This paper compares the performance of Black–Scholes with an artificial neural network (ANN) in pricing European‐style call options on the FTSE 100 index. It is the first extensive study of the performance of ANNs in pricing UK options, and the first to allow for dividends in the closed‐form model. For out‐of‐the‐money options, the ANN is clearly superior to Black–Scholes. For in‐the‐money options, if the sample space is restricted by excluding deep in‐the‐money and long maturity options (3.4% of total volume), then the performance of the ANN is comparable to that of Black–Scholes. The superiority of the ANN is a surprising result, given that European‐style equity options are the home ground of Black–Scholes, and suggests that ANNs may have an important role to play in pricing other options for which there is either no closed‐form model, or the closed‐form model is less successful than is Black–Scholes for equity options. Copyright © 2005 John Wiley & Sons, Ltd.
The prediction of profitability using accounting narratives: a variable‐precision rough set approach
Authors: Beynon Malcolm J. , Clatworthy Mark A. , Jones Michael John
Published: May 2005

This article utilizes a new method of data mining for the classification of companies as profitable or non‐profitable, based on a textual analysis of the respective chairman's statement. The method used is a development of the rough set theory technique, namely the variable‐precision rough sets (VPRS) model. A dichotomous sample of companies is used to construct a set of decision rules from a VPRS analysis using the textual characteristics of the chairman's statement in UK corporate annual reports. A number of descriptive measures are analyzed, including the predictive accuracy of the decision rules. Copyright © 2005 John Wiley & Sons, Ltd.
Fabrication, implantation, elution, and retrieval of a steroid‐loaded polycaprolactone subretinal implant
Authors: Beeley Nathan R. F. , Rossi Juliana V. , Mello‐Filho Paulo A. A. , Mahmoud Mahmoud I. , Fujii Gildo Y. , de Juan Eugene , Varner Signe E.
Published: May 2005

A subretinal drug delivery system was developed to overcome the limitations of current treatments for retinal disease. A rod‐shaped implant was made by embedding the corticosteroid triamcinolone acetonide within a biodegradable polycaprolactone polymer matrix. The implant was fabricated by homogenously mixing the polymer and drug in solvent. The mixture was then dried, melted, and extruded, and the prepared solid form was drawn into a filament. The rods were mechanically sectioned to a length of 2 mm with a diameter of up to 320 μm. The rods were successfully implanted into the subretinal space of six rabbits. No complications were observed during the 4‐week follow‐up period. Initial observations of the implantation and elution characteristics revealed that polycaprolactone is well tolerated by the retinal tissue and that the implant can elute steroid for a period of at least 4 weeks without eliciting inflammatory response or complications. In vitro drug elution rates of different polymer to drug ratios and geometries into a balanced salt solution/bovine serum albumin (1%) solution showed an early rapid‐release phase and late first‐order phase. Histology and device retrieval after implantation revealed minimal encapsulation and good preservation of cellular morphology during the follow‐up period and a more fibrous polymer microstructure of the implant. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Association of IL‐1Ra gene polymorphism, but no association of IL‐1β and IL‐4 gene polymorphisms, with Kawasaki disease
Authors: Wu Shu‐Fen , Chang Jeng‐Sheng , Wan Lei , Tsai Chang‐Hai , Tsai Fuu‐Jen
Published: May 2005

The purpose of this study was to evaluate whether IL‐1 β (IL‐1β promoter and IL‐1β exon 5), IL‐1 receptor antagonist (IL‐1 Ra), and IL‐4 (IL‐4 promoter and IL‐4 intron 3) gene polymorphisms act as markers of susceptibility to Kawasaki disease (KD), or of the severity of the disease. The study included 107 KD patients and 103 normal controls. Polymorphisms for cytokine genes were detected by polymerase chain reaction (PCR). Genotypes and allelic frequencies for cytokine gene polymorphisms in both groups were compared. No significant difference was observed in the genotypes and allelic frequencies of cytokines between patients with coronary aneurysm and without. In addition, there was no significant association in the genotype and allelic frequencies of IL‐1 beta, IL‐4, and IL‐6 in patients with KD. The genotype I/II for IL1‐Ra and the frequency of allele II for IL1‐Ra are associated with a higher susceptibility to KD, and thus may be useful markers for predicting the development of KD. J. Clin. Lab. Anal. 19:99–102, 2005. © 2005 Wiley‐Liss, Inc.
Usefulness of high‐sensitivity IL‐6 measurement for clinical characterization of patients with coronary artery disease
Authors: Lubrano Valter , Cocci Franca , Battaglia Debora , Papa Angela , Marraccini Paolo , Zucchelli Gian Carlo
Published: May 2005

Interleukin 6 (IL‐6) may represent an early marker of inflammatory activation and may be useful to ameliorate risk stratification in patients with ischemic heart disease. The aim of this study was to verify the performance characteristics of an ultrasensitive immunoassay (Biosource International, Camarillo, CA) for high‐sensitivity (hs)‐IL‐6 measurement in comparison with hs‐R&D Systems (Abingdon, United Kingdom) and Immulite System (Diagnostic Products Corporation [DPC], Los Angeles, CA) methods in patients with ischemic heart disease. In addition, hs–C‐reactive protein (hs‐CRP) concentrations were measured, to evaluate the correlation with hs‐IL‐6 levels. We measured IL‐6 and CRP serum levels in 39 patients with ischemic heart disease and in 12 controls. Out of the 39 patients studied, 13 were affected by unstable angina, 13 by post–acute myocardial infarction (AMI) unstable angina, and 13 by stable angina. The imprecision profile and functional sensitivity were performed measuring 9 different serum pools in 10 runs. The Biosource method had the best performance characteristics as compared to the others. Mean IL‐6 level was higher in patients with unstable and post‐AMI unstable angina with respect to controls. CRP levels were elevated in patients with post‐AMI. In the whole population a high significant linear regression was observed between Biosource hs‐IL‐6 and hs‐CRP serum levels. The Biosource method for IL‐6 measurement is characterized by a high functional sensitivity that allows a better stratification of patients with ischemic heart disease. J. Clin. Lab. Anal. 19:110–114, 2005. © 2005 Wiley‐Liss, Inc.
Influence of protein binding on acrolein turnover in vitro by oxazaphosphorines and liver microsomes
Authors: Baumann Frank , Schmidt Renate , Teichert Jens , Preiss Rainer
Published: May 2005

For a correct determination of acrolein amounts generated in in vitro turnover experiments with oxazaphosphorines, it is necessary to characterize the interaction of acrolein with liver microsomal proteins. Acrolein, a highly reactive metabolite of oxazaphosphorines, readily forms covalent adducts with proteins by electrophilic attack on nucleophiles, such as the sulfhydryl group of cysteine, imidazole group of histidine, and amino group of lysine. The current investigations were mainly directed toward determination of the degree of acrolein‐protein binding under conditions of in vitro experiments with liver microsome preparations. The acrolein concentration in protein dilution was determined by a fluorescence method. Moreover, the influence of sucrose and glycerine on the extent of acrolein‐protein binding commonly used for the stabilization of microsomal preparations during storage was investigated. The current investigations show evidence that the chemical reaction of acrolein with liver microsomal proteins strictly follows first order kinetics. The main part of the formed acrolein in the in vitro attempts is available as bound part. Results of these investigations indicate that the calibration should be carried out with mixtures from liver microsome preparations and known amounts of acrolein under the same conditions as the in vitro experiments to record the entirely formed acrolein part (free and bound) in oxazaphosphorine turnover experiments. Glycerine is recommended as a preservative to store liver microsomes instead of sucrose because the latter reacts with acrolein. J. Clin. Lab. Anal. 19:103–109, 2005. © 2005 Wiley‐Liss, Inc.
Interferon‐gamma, tumor necrosis factor‐alpha, and lipopolysaccharide promote chitotriosidase gene expression in human macrophages
Authors: Malaguarnera L. , Musumeci M. , Di Rosa M. , Scuto A. , Musumeci S.
Published: May 2005

Human chitotriosidase (Chit), a chitinolytic enzyme, is a member of the chitinase family. In human plasma, Chit activity has been proposed as a biochemical marker of macrophage activation in several lysosomal diseases. Recently we found that Chit activity is higher in patients affected by Plasmodium falciparum malaria infection, suggesting that Chit may reflect induction of an immunological response. To assess this hypothesis, we evaluated the CHIT1 mRNA levels in human monocytes/macrophages (HMMs) following treatment with interferon‐gamma (IFNγ), tumor necrosis factor‐alpha (TNFα), and lipopolysaccharide (LPS). Stimulation of macrophages with INF‐γ, TNF‐α, and LPS resulted in an increase in Chit activity as well as the levels of CHIT1 mRNA as measured by quantitative real‐time PCR. The data presented in this article show that Chit plays a role in the response to the activation of INF‐γ‐, TNF‐α‐, and LPS‐driven macrophages, suggesting that the production of Chit by macrophages could have biological relevance in the immune‐response. J. Clin. Lab. Anal. 19:128–132, 2005. © 2005 Wiley‐Liss, Inc.
Validity of analysis of FMRP expression in blood smears as a screening test for Fragile X Syndrome in the Indian population
Authors: Ravindran M. Shyla , Patel Zareen M. , Adhia Rashmi A. , D'souza Aruna K. , Babu Shiny
Published: May 2005

Molecular diagnosis of Fragile X Syndrome (FXS) is carried out by PCR or Southern blot analysis on DNA isolated from leukocytes. These DNA analyses are time consuming and expensive, making it impractical for mass screening programs. We have recently standardized and tested the diagnostic potential of a rapid antibody test on blood smears, based on the presence of FMRP, the protein product of the FMR1 gene, in lymphocytes from normal individuals and the absence of FMRP in lymphocytes in patients with FXS. This test is essentially similar to the one developed at Erasmus University in the Netherlands, with suitable modifications. The diagnostic power of the antibody test is perfect for males, whereas the results are less specific for females. The cutoff value for affected male individuals, expressed as the percentage of FMRP‐positive cells, was 20%. In normal individuals, the cutoff value was 85%. The results of the antibody test correlated well with that of Southern blots. Sensitivity of the test was 100% and specificity was 97.5%. This noninvasive test requires one or two drops of blood and is rapid, simple, and cheap, making it an ideal choice for large screening large groups of male mental retardates and neonates for FXS in developing countries such as India. J. Clin. Lab. Anal. 19:120–123, 2005. © 2005 Wiley‐Liss, Inc.
The role of potassium as an ionic signal in the regulation of cyanobacterium Nostoc muscorum response to salinity and osmotic stress
Authors: Bhargava Santosh
Published: May 2005

Spontaneously occurring thallium‐resistant (Tl+‐R) mutant of diazotrophic, heterocystous cyanobacterium Nostoc muscorum is described in which Tl+‐R phenotype is the cause of defective salinity‐inducible K+ uptake activity and proline uptake activity. The results indicate that mutant strain is more sensitive to salinity and osmotic stresses than its parent. The mutational inactivation of salinity‐inducible proline uptake was found associated with increased sensitivity of the cyanobacterial photosynthetic O2 evolution and nitrogenase activity under salinity and osmotic stresses. It is suggested that in the cyanobacterium Nostoc muscorum K+ functions as a primary osmolyte which is associated with salinity‐inducible proline uptake leading to the acquisition of salt tolerance in the cyanobacterium. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Excitation and propagation of surface electromagnetic waves studied by terahertz spectrochronography
Authors: Nazarov M M , Mukina L S , Shuvaev A V , Sapozhnikov D A , Shkurinov A P , Trofimov V A
Published: May 2005

We show the spectrochronography as an efficient tool to extend the THz time domain technique. Assuming that all the information is contained in the time-dependent electric field we apply a windowed transfer technique to measure the instantaneous spectra evolution. As an example, surface electromagnetic waves on the metal grating are considered. Dynamics of surface wave spectral component is measured.
Two-photon near-field mapping of local molecular orientations in hexaphenyl nanofibers
Authors: Beermann J , Bozhevolnyi S I , Balzer F , Rubahn H-G
Published: May 2005

Two-photon excited near field images of hexaphenyl
nanofibers are obtained using a scanning near field optical
microscope in transmission configuration. From polarized
measurements the orientations of the molecular basis units of the
fibers are determined with a resolution of better than 400 nm. The
molecular orientation angles obtained are comparable to results
from two-photon scanning far-field microscopy, but the present
measurements provide a better spatial resolution. From this
near-field data it is concluded that the molecules can be oriented
either very homogeneously or with some scatter in otherwise
similar organic nanoaggregates.
Nonlinear resonant change in refractive index of a doped saturable
medium at short-pulse excitation
Authors: Kir'yanov A V , Il'ichev N N
Published: May 2005

A novel method is reported for calculating the
nonlinear resonant change in refractive index of a doped saturable
medium at the short-pulse excitation. The derived system of
equations for energy density and phase of a short pulse
propagating in the doped medium allows one to address a rather
general case of the resonant index non-linearity caused by the
dope's population perturbation (bleaching) effect. As an example,
the energy-dependent changes in the refractive index and
transmission coefficient of a Cr4+:YAG crystal under the
ns-range (wavelength 1.06 μm) excitation are modeled.
Metathetic Selective Degradation of Polyisoprene: Low‐Molecular‐Weight Telechelic Oligomer Obtained from Both Synthetic and Natural Rubber
Authors: Solanky Shailendra Singh , Campistron Irène , Laguerre Albert , Pilard Jean‐François
Published: May 2005

Summary: Degradation studies of cis‐1,4‐polyisoprene were carried out using first and second generation Grubbs catalysts to achieve end‐functionalized acetoxy oligomers in both an organic solvent and a latex phase at room temperature. Well‐defined acetoxy telechelic polyisoprene structures were obtained in a selective manner with a range of $\overline M _{\rm n}$ from 10 000 to 30 000, with a polydispersity index of around 2.5.

Structure produced by the metathetic depolymerization of hydroxy telechelic cis‐1,4‐polyisoprene.

magnified image

Structure produced by the metathetic depolymerization of hydroxy telechelic cis‐1,4‐polyisoprene.
Synthesis and Characterization of Macrocyclic Vinyl‐Aromatic Polymers.
Authors: Alberty Kurt A. , Hogen‐Esch Thieo E. , Carlotti Stephane
Published: May 2005

Summary: Matching macrocyclic and linear polystyrenes (PS) were synthesized by the initiation of styrene with 2,7‐dimethyl‐3,6‐diphenyloctane dianion lithium salt followed by high dilution coupling with 1,4‐bis(bromomethyl)benzene or protonation. Liquid chromatography at the critical condition shows the presence of less than 4% of linear PS impurities in the fractionated cycles. SEC studies confirm that the ratios of apparent MWs of cyclic and linear PS increase from about 0.7 to more than 0.9 as MWs decrease. Fluorescence studies show that the monomer emissions at 285 nm strongly increase with decreasing MW whereas those of the linear polymers are not significantly affected. This may be due in part to the increased rigidity of the smaller cycles that decreases the rate of radiation‐less deactivation.

Dependence of 〈G〉 on number average MW.

magnified image

Dependence of 〈G〉 on number average MW.
Comparison of Styrene with Methyl Methacrylate Copolymers on the Adhesive Performance and Peeling Master Curves of Acrylate Pressure Sensitive Adhesives
Authors: Gower Mark D. , Shanks Robert A.
Published: May 2005

Summary: Styrene (S) and methyl methacrylate (MMA) copolymers were prepared with acrylates, such as butyl acrylate, 2‐ethylhexyl acrylate and acrylic acid, for application as pressure sensitive adhesives (PSA). The copolymer compositions were designed to provide constant glass transition temperature. The PSA were tested using peel adhesion resistance, static shear resistance, loop tack and DMA. Time‐temperature‐superposition (TTS) was used to construct peel resistance master curves to compare copolymers containing S and MMA, and obtain a structural interpretation of the PSA performance. The TTS master curves were combined for related copolymer series to obtain composition super master curves. The super master curve construction demonstrated the comonomer composition dependence of the PSA performance and distinguished copolymers containing S from those containing MMA. Composition related performance was exhibited by static shear and loop tack, the latter in relation to the concentration shift factors. DMA results confirmed the adhesive performance interpretations. Composition super master curves suggested differences in the relative mobility of S and MMA copolymers. Chain branching and entanglements were more significant with MMA than with S copolymers. DMA and static shear resistance confirmed the peel resistance results. S copolymers decreased the loop tack consistent with their higher molecular weight and lower polydispersity, with fewer low molecular weight fractions contributing to the tack. MMA copolymers dissipated more energy under high stress than S copolymers.

Example peel master curve for formulation AA4M91‐2 (reference temperature: T0 = 298 K).

magnified image

Example peel master curve for formulation AA4M91‐2 (reference temperature: T0 = 298 K).
Novel Poly(butylene succinate)‐Based Ionomers with Sulfonated Succinate Units: Synthesis, Morphology, and the Unique Nucleation Effect on Crystallization
Authors: Ishida Kazuki , Han Sang‐Il , Inoue Yoshio , Im Seung‐Soon
Published: May 2005

Summary: Poly(butylene succinate) (PBS) and PBS‐based ionomers (PBSi's) with 0.3 and 1.2 mol‐% of sodium sulfonated succinate unit were synthesized. The existence of ionic aggregates in the ionomer matrices was indicated by melt viscosity and glass transition data. It seems that the ionic aggregates have two opposing roles in crystallization: one is the induction of nucleation and the other is the interference with lamellar growth. Because of these two contrary effects, the crystallization behavior of the ionomers exhibited measurably different cooling rate‐dependencies than that of the parent PBS. The rate varied distinctly with ionic content.

Spherulitic morphologies of PBS and PBSi's measured with polarizing optical microscopy.

magnified image

Spherulitic morphologies of PBS and PBSi's measured with polarizing optical microscopy.
Ethylene–Propylene Copolymerisations: Effect of Metallocene Structure on Termination Reactions and Polymer Microstructure
Authors: Tynys Antti , Saarinen Tapio , Hakala Kimmo , Helaja Tuulamari , Vanne Tiina , Lehmus Petri , Löfgren Barbro
Published: May 2005

Summary: Ethylene–propylene (EP) copolymerisations were performed with two sterically different metallocenes activated by methylaluminoxane (MAO) in an attempt to better understand the effect of catalyst structure on termination reactions and polymer microstructure. The metallocene precursors under investigation were rac‐dimethylsilylbis(2‐methyl‐4‐phenyl‐1‐indenyl)zirconium dichloride (1) and a more sterically hindered counterpart rac‐dimethylsilylbis(2‐isopropyl‐4‐[3,5‐dimethylphenyl]indenyl) zirconium dichloride (2). For both catalyst systems, the most common termination mechanism was chain transfer to aluminium. In addition, for polymer samples polymerised with 1/MAO, chain growth was terminated by chain transfer to Zr metal in propylene‐rich polymerisations and by chain transfer to ethylene monomer in ethylene‐rich polymerisations. The steric hindrance of 2 was able to suppress the chain transfer to the ethylene monomer, and chain transfer to Zr metal was also found in the ethylene‐rich polymerisations. The greater steric hindrance of 2 also affected the EP copolymer microstructure: regioregularity in the propylene‐rich copolymers was greater and isotacticity less with 2/MAO than with 1/MAO.

The catalyst precursors used: rac‐dimethylsilylbis(2‐methyl‐4‐phenyl‐1‐indenyl)zirconium dichloride (1) and rac‐dimethylsilylbis(2‐isopropyl‐4‐[3,5‐dimethylphenyl]indenyl) zirconium dichloride (2).

magnified image

The catalyst precursors used: rac‐dimethylsilylbis(2‐methyl‐4‐phenyl‐1‐indenyl)zirconium dichloride (1) and rac‐dimethylsilylbis(2‐isopropyl‐4‐[3,5‐dimethylphenyl]indenyl) zirconium dichloride (2).