bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial resolution sensitivity of catchment geomorphologic properties and the effect on hydrological simulation
Authors: Yang Dawen , Herath Srikantha , Musiake Katumi
Published: September 2002

The geomorphologic area function and width function that characterize the forms of hillslope and river networks are two key parameters employed in the GBHM (geomorphology‐based hydrological model) for representing the hydrological processes together with other spatial information. One fundamental issue on the use of the geomorphologic properties is the spatial resolution sensitivity in both the threshold area for river network generation and digital elevation model (DEM) resolution. The threshold area is the minimum drainage area required to initiate the river; the DEM resolution depends on the available elevation data. In the present study, multifractal analysis was used to investigate the sensitivity of width functions extracted by different threshold areas and the sensitivity of area functions extracted from various resolutions of DEMs. Fifteen Japanese catchments were selected for the sensitivity analysis based on 250 m mesh DEM data. It was found that the river networks generated with larger threshold areas tend to lose the detailed scaling information. When the DEM mesh size increases, the river networks extracted with the same threshold area become sparser and the topography tends to be flat and scaling structures of the area functions become simpler. The runoff generations of the GBHM were influenced by the DEM resolution. The effect of the DEM resolution on the hydrological response is related to the temporal resolution with more influence on the hourly response compared with the daily response. From the relation between the scaling structure expressed by the multifractal spectrum and the hydrological response of a catchment, it was found that the detailed scaling information had more effect on the hydrological response of higher temporal resolution. Copyright © 2001 John Wiley & Sons, Ltd.
Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome
Authors: Sgambato Alessandro , Migaldi Mario , Faraglia Beatrice , De Aloysio Graziella , Ferrari Paolo , Ardito Raffaele , De Gaetani Carmela , Capelli Giovanni , Cittadini Achille , Trentini Gian Paolo
Published: September 2002

Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin‐dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa‐pT1) bladder cancers and was correlated with p27Kip1, p21Waf1 and c‐erbB‐2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (≥25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21Waf1 (p = 0.015) and high p27Kip1 (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (≥10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease‐free survival (p < 0.001 by log‐rank test). Increased Ki67 expression was significantly associated with shorter disease‐free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease‐free survival on a multivariate analysis that also included p27Kip1 expression and tumor stage. The simultaneous presence of low cyclin D1, low p27Kip1 and high Ki67 expression defined a “high‐risk” group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle‐associated markers can help to identify high‐risk patients and may affect the management of patients with papillary superficial bladder cancer. © 2001 Wiley‐Liss, Inc.
Testicular hyaluronidase induces tubular structures of endothelial cells grown in three‐dimensional colagen gel through a CD44‐mediated mechanism
Authors: Rahmanian Mehdi , Heldin Paraskevi
Published: September 2002

Cultured brain capillary endothelial cells grown in a 3‐dimensional collagen gel can form tubular structures after stimulation by angiogenic factors. We found that treatment of such cultures with testicular hyaluronidase led to formation of tubular structures and cell survival. Anion‐exchange chromatography of the enzyme preparation on a MonoQ column revealed the presence of the angiogenic factor basic fibroblast growth factor (bFGF) in the flow‐through fraction, as determined by immunoblotting; part of the effect on endothelial cell morphogenesis could thus be ascribed to bFGF. However, adsorbed fractions eluted with increasing concentrations of NaCl, which exhibited hyaluronan‐degrading activity at neutral pH, did not contain bFGF but were still able to induce tube‐like structures of the endothelial cells. Streptomyces hyaluronidase failed to evoke the same effect. Interestingly, blocking of hyaluronan binding to CD44 receptors by the monoclonal antibody KM114 inhibited the effect of hyaluronidase, but not of bFGF, on endothelial cell tube formation. Our data suggest a CD44‐mediated specific role for certain populations of testicular hyaluronidase in the induction of angiogenesis. © 2001 Wiley‐Liss, Inc.
Upregulation of bcl‐2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines
Authors: Sartorius Ute A. , Krammer Peter H.
Published: September 2002

Chemotherapeutic drugs eliminate cancer cells by induction of apoptosis. Resistance to chemotherapy is partly due to a decreased apoptosis rate. Here we investigated resistance to anticancer drugs in 9 small cell lung cancer (SCLC) cell lines. Apoptosis was induced by cisplatin, doxorubicin and etoposide and was found to be independent of caspase‐8 expression. Since caspase‐8 is essential for signal transduction of death receptor‐mediated apoptosis, all known death receptor systems are thus not required for drug‐induced apoptosis in SCLC. Furthermore, we found that anticancer drugs could activate the mitochondrial pathway of apoptosis without involvement of upstream caspases. Finally, by culturing 3 sensitive cell lines in subtherapeutic concentrations of etoposide, resistant cells were generated that exhibit cross‐resistance to cisplatin and doxorubicin. Drug resistance was paralleled by strong upregulation of Bcl‐2, which diminished apoptosis by inhibiting the loss of the mitochondrial transmembrane potential and the release of cytochrome c. The role of bcl‐2 in these processes was supported by bcl‐2 transfection and antisense inhibition. These results indicate that Bcl‐2 contributes to drug resistance in SCLC, a finding that has profound therapeutic implications. © 2001 Wiley‐Liss, Inc.
Involvement of hMSH6 in the development of hereditary and sporadic colorectal cancer revealed by immunostaining is based on germline mutations, but rarely on somatic inactivation
Authors: Plaschke Jens , Krüger Stefan , Pistorius Steffen , Theissig Franz , Saeger Hans D. , Schackert Hans K.
Published: September 2002

Germline mutations in human mismatch repair (MMR) genes yield a predisposition for the hereditary nonpolyposis colon cancer (HNPCC) syndrome. In contrast to hMLH1 and hMSH2, little is known about the overall involvement of hMSH6 in colorectal cancer. We investigated 82 tumors from patients who fulfilled the Bethesda guidelines for HNPCC as well as 146 sporadic tumors, analyzing microsatellite instability and expression of the 4 MMR proteins hMSH6, hMSH2, hMLH1 and hPMS2. Four tumors with lost expression and 1 tumor with cytoplasmic expression of hMSH6 were identified. Sequence analysis revealed germline mutations in 4 of the 5 patients, including 1 patient with sporadic disease. The lost or reduced expression of hMSH2 and hMLH1 was always identical to its heterodimerization partners, hMSH6 and hPMS2, respectively. Furthermore, hMSH2 expression was reduced upon hMSH6 deficiency. Abnormal expression of 1 or more of the 4 proteins was always associated with a high level of microsatellite instability (MSI‐H). Conversely, all but 1 of the 44 MSI‐H tumors had abnormal expression of 1 or more of the proteins, basically excluding additional genes associated with the MSI‐H phenotype. We conclude that the involvement of somatic or epigenetic hMSH6 inactivation in colorectal cancer is rare. © 2001 Wiley‐Liss, Inc.
Modulation of HMG‐N2 binding to chromatin by butyrate‐induced acetylation in human colon adenocarcinoma cells
Authors: Lührs Hardi , Hock Robert , Schauber Jürgen , Weihrauch Marc , Harrer Monika , Melcher Ralph , Scheppach Wolfgang , Bustin Michael , Menzel Thomas
Published: September 2002

Butyrate, a short chain fatty acid (SCFA), is generated by anaerobic fermentation of undigested carbohydrates within the colon. Butyrate enhances acetylation of core histones, a process directly linked to the formation of active chromatin and gene expression. However, additional chromatin components also contribute to the formation of transcriptionally active chromatin. The high mobility group protein N2 (HMG‐N2), a nonhistone protein, is involved in chromatin structure modulation. We examined the effects of butyrate on HMG‐N2 expression, hyperacetylation and chromatin binding. HT29 human adenocarcinoma cells were incubated with butyrate. Levels of HMG‐N2 mRNA and of total or acetylated HMG‐N2 protein were analyzed. Protein dynamics were investigated with transfected cells expressing HMG‐N2‐EGFP fusion proteins. Treatment of HT29 cells with butyrate led to significant hyperacetylation of HMG‐N2. Levels of HMG‐N2 protein remained unchanged. Northern blot analysis revealed a significant reduction in HMG‐N2 mRNA levels after treatment with butyrate. Analysis of HMG‐N2‐EGFP transfected HT29 cells demonstrated that butyrate treatment changes the binding properties of HMG‐N2‐EGFP to chromatin. In addition, butyrate treatment resulted in solubilization of endogenous acetylated HMG‐N2 into the supernatant of permeabilized cells. We demonstrate that butyrate treatment is associated with hyperacetylation of HMG‐N2 protein in HT29 cells. The modulation of this nonhistone chromatin protein resulted in altered binding properties to chromatin. This may represent an additional step in changing chromatin structure and composition with subsequent consequences for transcription and gene expression. Modulation of nonhistone chromatin proteins, like the ubiquitous HMG‐N2 proteins, may be partly responsible for the wide range of butyrate‐associated effects. © 2001 Wiley‐Liss, Inc.
Oxidant‐antioxidant status in relation to survival among breast cancer patients
Authors: Saintot Monique , Mathieu‐Daude Hélène , Astre Cécile , Grenier Jean , Simony‐Lafontaine Joelle , Gerber Mariette
Published: September 2002

The role of plasma oxidant‐antioxidant status in survival after breast cancer surgery was investigated in a cohort of patients (n = 363) hospitalized in Southern France between 1989 and 1992. The median follow‐up was 8 years after surgery for histologically confirmed breast cancer. Plasma analyses were performed after diagnosis and before surgery and adjuvant therapy. We found an inverse relationship between plasma lipoperoxides (MDA) and tumor size at diagnosis, together with higher lipoperoxide levels in node‐negative tumors than in node‐positive ones (TNM). The longitudinal approach revealed an increased risk of recurrence for patients with plasma lipoperoxides in the highest tertile of the sample (RR = 2.1, 95%CI 1.1–4.0). In addition, the risk of recurrence increased (RR = 1.7, 95%CI 1.0–3.0), after adjustment for the known prognostic factors (TNM), for patients with plasma lipid‐adjusted vitamin E levels of over 22 μmol/l. The risk of breast cancer death was twice as great for patients with plasma lipid‐adjusted vitamin E levels above this value. Excesses of plasma lipoperoxides and vitamin E appear to be factors in poor prognosis for breast cancer‐specific survival (OVS) and disease‐free survival (DFS), respectively, independent of tumor characteristics at diagnosis. Several hypotheses are advanced to explain the possible role of plasma vitamin E as a factor in poor prognosis for survival. © 2001 Wiley‐Liss, Inc.
Inhibition of both skin and lung tumorigenesis by Car‐R mouse‐derived cancer modifier loci
Authors: Saran Anna , Zaffaroni Daniela , Pazzaglia Simonetta , Peissel Bernard , Galbiati Federica , Spinola Monica , Manenti Giacomo , Zanesi Nicola , Rebessi Simonetta , Mancuso Maria Teresa , Covelli Vincenzo , Dragani Tommaso A.
Published: September 2002

The Car‐R outbred mouse line was phenotypically selected for high resistance to two‐stage skin tumorigenesis. In the present study we tested the hypothesis that a subset of genetic loci responsible for resistance to skin tumorigenesis of Car‐R mice might also inhibit lung tumorigenesis. Skin and lung tumorigenesis were induced in groups of Car‐R, SWR/J, (SWR/JxCar‐R)F1 and SWR/Jx(SWR/JxCar‐R) backcross mice by i.p. urethane initiation and skin TPA promotion. Car‐R mice showed a much lower susceptibility to both skin and lung tumorigenesis as compared to SWR/J mice, which are susceptible to both lung and skin tumorigenesis. The Car‐R‐inherited genome significantly inhibited both skin and lung cancer development in the F1 progeny of Car‐R with SWR/J mice. In the backcross population, skin and lung tumor phenotypes showed a statistically significant correlation, indicating that a subset of the cancer resistance alleles, which segregated in the Car‐R line during selection for resistance to skin carcinogenesis, provides resistance to both skin and lung tumorigenesis. © 2001 Wiley‐Liss, Inc.
Expression of uridine and thymidine phosphorylase genes in human breast carcinoma
Authors: Kanzaki Atsuko , Takebayashi Yuji , Bando Hiroko , Eliason James F. , Watanabe Shin‐ichi , Miyashita Hitoshi , Fukumoto Manabu , Toi Masakazu , Uchida Takafumi
Published: September 2002

Uridine phosphorylase (UPase) and an angiogenic enzyme, thymidine phosphorylase (dThdPase) are involved in degradation of the pyrimidine nucleosides through phosphorolysis. The expression levels of UPase and dThdPase are higher in human solid tumors including breast carcinomas than in normal tissues. To clarify the correlation between the expression levels of UPase and dThdPase genes and the clinicopathological factors, mRNA levels of these enzymes were examined by RT‐PCR in 43 breast carcinomas. UPase gene expression was not correlated with dThdPase gene expression (regression coefficient R = 0.032). Although the expression level of the dThdPase gene was correlated with angiogenesis, detected by immunostaining endothelial cells (R = 0.66), that of UPase gene was not (R = 0.044). These results suggest that UPase does not have a strong angiogenic activity. The UPase gene expression levels in tumors of patients who relapsed were significantly higher than in those from patients who did not (p = 0.039). Although the expression levels of neither UPase or dThdPase were associated with age, pT, pN, pM, estrogen or progesterone receptor positivity, the patients with the higher levels of UPase gene expression had worse survival (p = 0.0038) than those with lower levels. In contrast, the expression of dThdPase gene was not related to relapse or survival of these patients with breast carcinoma. Our findings suggest that the expression level of UPase gene may be an independent prognostic marker in human breast carcinoma. © 2001 Wiley‐Liss, Inc.
Evidence of haplotype insufficiency in human cells containing a germline mutation in BRCA1 or BRCA2
Authors: Buchholz Thomas A. , Wu Xifeng , Hussain Abu , Tucker Susan L. , Mills Gordon B. , Haffty Bruce , Bergh Sherry , Story Michael , Geara Fady B. , Brock William A.
Published: September 2002

The BRCA1 and BRCA2 gene products are thought to play important roles in the processing of DNA damage. To assess whether heterozygous mutations in these genes are associated with cellular radiosensitivity, we performed an in vitro radiation clonogenic survival assay on dermal fibroblasts obtained from 8 sequence‐proven BRCA heterozygotes (6 BRCA1, 2 BRCA2). These data were compared to results obtained from a previous set of 17 prospectively studied cancer patients who had a negligible risk for a BRCA mutation. In addition, results from radiation‐induced chromatid break assay performed on lymphocytes obtained from 9 BRCA heterozygotes (8 BRCA1, 1 BRCA2) were compared to results from a control group of 18 women with no cancer history. Results from both assays suggested that cells containing a heterozygous mutation in BRCA1 or BRCA2 were more radiosensitive than controls. For the fibroblast studies, the mean surviving fraction at 2 Gy (SF2) for carriers was 0.279 vs. 0.348 for the control set (p = 0.007). For the lymphocyte studies, the mean number of chromatid breaks after 125 cGy of radiation was 0.79 breaks per cell for the carriers vs. 0.45 for the controls (p = 0.0005). There was no apparent difference in the radiosensitivity between cells with BRCA1 vs. BRCA2 mutations (p = 0.769), although the small sample size minimizes the certainty of this observation. These preliminary results are consistent with a relationship between a germline mutation in BRCA1 or BRCA2 and a hypersensitivity to radiation. This phenotype could possibly predispose to an increased risk of radiation‐induced mutagenesis and carcinogenesis. © 2001 Wiley‐Liss, Inc.
Prevalence of high‐risk human papilloma virus types and its association with P53 codon 72 polymorphism in tobacco addicted oral squamous cell carcinoma (oscc) patients of Eastern India
Authors: Nagpal Jatin K. , Patnaik Srinivas , Das Bibhu R.
Published: September 2002

Human papillomavirus (HPV) infects the squamous epithelial cells of oral cavity and cervix leading to formation of warts that develops into the cancer. Human papillomavirus (HPV)‐16 and 18 encode E6 oncoprotein, which binds to and induces degradation of the tumour suppressor protein p53. A common polymorphism of p53, encoding either proline (Pro) or arginine (Arg) at position 72, affects the susceptibility of p53 to E6 mediated degradation in vivo. Oral cancer is a pressing problem in India due to the widespread habit of chewing betel quid, which plays an important role in etiology of this disease. In the present study an attempt has been made to analyze the genetic predisposition of the Indian population to HPV infection and oral carcinogenesis. In our study a total of 110 cases of Oral Cancer highly addicted to betel quid and tobacco chewing are analyzed for HPV 16/18 infection and its association with polymorphism at p53 codon 72. Of these a total number of 37 patients (33.6%) have shown the presence of HPV, among which the presence of HPV‐16, 18 and 16/18 coinfection is 22.7%, 14.5% and 10%, respectively. Our results also indicate that the p53 codon 72 genotype frequencies in Indian Oral Cancer patients are 0.55 (Arg) and 0.45 (Pro) as per Hardy‐Weinberg equilibrium. In our study, striking reduction in Pro/Pro allele frequency has been found in HPV positive cases, indicating Arg/Arg genotype to be more susceptible to HPV infection and oral carcinogenesis. © 2001 Wiley‐Liss, Inc.
Establishment of a non‐tumorigenic papillary thyroid cell line (FB‐2) carrying the RET/PTC1 rearrangement
Authors: Basolo Fulvio , Giannini Riccardo , Toniolo Antonio , Casalone Rosario , Nikiforova Marina , Pacini Furio , Elisei Rossella , Miccoli Paolo , Berti Piero , Faviana Pinuccia , Fiore Lisa , Monaco Carmen , Pierantoni Giovanna Maria , Fedele Monica , Nikiforov Yuri E. , Santoro Massimo , Fusco Alfredo
Published: September 2002

A novel human thyroid papillary carcinoma cell line (FB‐2) has been established and characterized. FB‐2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB‐2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI‐C and c‐myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB‐2 cells but not in normal thyroid cells. FB‐2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX‐8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH‐receptor and thyroperoxidase genes were not. Moreover, FB‐2 cells produced high levels of interleukin (IL)‐6 and IL‐8. © 2001 Wiley‐Liss, Inc.
A sequence repeat in the insulin‐like growth factor‐1 gene and risk of breast cancer
Authors: Missmer Stacey A. , Haiman Christopher A. , Hunter David J. , Willett Walter C. , Colditz Graham A. , Speizer Frank E. , Pollak Michael N. , Hankinson Susan E.
Published: September 2002

Insulin‐like growth factor‐1 (IGF‐I), a potent mitogen, is hypothesized to influence breast cancer risk. In 3 previous studies, a polymorphism in the IGF‐1 gene (sequence repeat length) was associated with plasma IGF‐I level. We evaluated prospectively the relationships among a (CA)n repeat polymorphism in the IGF‐1 gene, IGF‐I level and breast cancer risk in a nested case‐control study conducted within the Nurses' Health Study. Blood samples were collected in 1989–1990; up to June 1994, we identified 463 cases of breast cancer. One to 2 controls were selected per case, matched by age, menopausal status, postmenopausal hormone use, month and time of day of blood collection and fasting status, for a total of 622 controls. Although no significant trend was observed, plasma IGF‐I levels were significantly lower among controls, with no copy of the 19 allele, compared with those homozygous for the 19 (CA)n repeat length (146 and 173 ng/ml, respectively; p‐value for pairwise mean comparison = 0.005). In conditional logistic regression, controlling for established breast cancer risk factors, we observed no significant association between (CA)n repeat length genotype and risk of breast cancer [compared with repeat genotype 19/19—18/19 genotype relative risk (RR) = 0.96, 95% confidence interval (CI) = 0.56–1.64; 18/20 genotype RR = 0.92, 95% CI = 0.39–2.19; 19/20 genotype RR = 1.16, 95% CI = 0.82–1.64; 19/21 genotype RR = 0.69, 95% CI = 0.42–1.14; 20/20 genotype RR = 0.55, 95% CI = 0.28–1.10; 20/21 genotype RR = 0.72, 95% CI = 0.29–1.79]. Results did not vary substantially when evaluated according to menopausal status, tumor receptor status or category of other breast cancer risk factors. Although a modest association cannot be excluded, our data do not support an important relation between this IGF‐1 gene polymorphism and breast cancer risk. © 2002 Wiley‐Liss, Inc.
Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers
Authors: Oji Yusuke , Miyoshi Shinichiro , Maeda Hajime , Hayashi Seiji , Tamaki Hiroya , Nakatsuka Shin‐Ichi , Yao Masayuki , Takahashi Eigo , Nakano Yoko , Hirabayashi Hirohisa , Shintani Yasushi , Oka Yoshihiro , Tsuboi Akihiro , Hosen Naoki , Asada Momotaro , Fujioka Tatsuya , Murakami Masaki , Kanato Keisuke , Motomura Mari , Kim Eui Ho , Kawakami Manabu , Ikegame Kazuhiro , Ogawa Hiroyasu , Aozasa Katsuyuki , Kawase Ichiro , Sugiyama Haruo
Published: September 2002

Expression of the Wilms' tumor gene WT1 in de novo lung cancer was examined using quantitative real‐time RT‐PCR and immunohistochemistry. Overexpression of the WT1 gene was detected by RT‐PCR in 54/56 (96%) de novo non‐small cell lung cancers examined and confirmed by detection of WT1 protein with an anti‐WT1 antibody. Overexpression of the WT1 gene was also demonstrated in 5/6 (83%) de novo small cell lung cancers by immunohistochemistry. Furthermore, when the WT1 gene was examined for mutations by direct sequencing of genomic DNA in 7 lung cancers, no mutations were found. These results suggest that the nonmutated, wild‐type WT1 gene plays an important role in tumorigenesis of de novo lung cancers and may provide us with the rationale for new therapeutic strategies for lung cancer targeting the WT1 gene and its products. © 2002 Wiley‐Liss, Inc.
Personality characteristics and the risk of breast cancer: A prospective cohort study
Authors: Lillberg Kirsi , Verkasalo Pia K. , Kaprio Jaakko , Helenius Hans , Koskenvuo Markku
Published: September 2002

Various personality characteristics have been suggested to increase the risk of breast cancer but reliable epidemiologic data on this issue are limited. We prospectively investigated the relationship between personality characteristics and the risk of breast cancer in 12,499 Finnish women aged 18 years or more. In health questionnaires in 1975 and 1981, these women completed at least one of the following personality scales: Eysenck extroversion, Bortner type A behaviour and author‐constructed measure of hostility. They also reported about other potential breast cancer risk factors. From 1976–1996, 253 cases of breast cancer were identified by record linkage with the Finnish Cancer Registry. Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The multivariable HRs of breast cancer for women with intermediate level (scores 3–6) and high level (7–9) of extroversion in 1975 were 1.18 (95% CI 0.87–1.60) and 0.97 (95% CI 0.64–1.47), respectively, compared to those with low level (0–2). These results remained unaltered when the level of extroversion was determined as the average of the 1975 and 1981 reports. There was also no increase in breast cancer risk in relation to type A behaviour and hostility. Furthermore, we observed no substantial joint effects of personality characteristics on the risk of breast cancer. In conclusion, our data do not support the existence of an important role for personality in the aetiology of breast cancer. These findings are reassuring to those who have believed the contrary. © 2002 Wiley‐Liss, Inc.
Cancer incidence among Sami in Northern Finland, 1979–1998
Authors: Soininen Leena , Järvinen Sari , Pukkala Eero
Published: September 2002

The Sami population living in Northern Finland represents a specific genetic background and a way of life that is different from other Finns. A cohort of 2,100 Sami and 4,174 non‐Sami people from the 2 northernmost municipalities of Finland on 31 December 1978 was identified from the national Population Register and followed up through the Finnish Cancer Registry for cancer incidence during 1979–1998. There were 111 cancer cases among the Sami, while the expected number based on the average cancer incidence in the Finnish population was 173. Among the non‐Sami cohort members, there were 226 cases of cancervs.224 expected cases. The Sami had significantly decreased incidence of cancers of the prostate [standardised incidence ratio (SIR) 0.25; 95% confidence interval (CI) 0.08–0.58] and breast (SIR 0.36; 95% CI 0.14–0.73), similarly for both localised and nonlocalised tumours. Low SIRs were also observed for bladder cancer (SIR 0.28; 97% CI 0.03–0.99) basal cell carcinoma of the skin (SIR 0.12; 95% CI 0.03–0.30) and other nonmelanoma skin cancers (SIR 0; 95% CI 0–0.63). In contrast to other subcategories of the Sami, the Skolts, whose lifestyle stems from areas that now belong to Russia, showed a nonreduced overall cancer risk and a significantly elevated risk for stomach cancer (SIR 3.8; 95% CI 1.5–7.8). The low cancer incidence among the other Sami populations in Finland cannot be fully explained by their specific way of life. It seems likely that the Sami ethnicity carries a reduced cancer incidence level. Although many Sami have been exposed to radioactive fallout from the nuclear weapon tests via their reindeer‐rich diet, this does not seem to affect their cancer risk. © 2002 Wiley‐Liss, Inc.
Increased emotional distress in daughters of breast cancer patients is associated with decreased natural cytotoxic activity, elevated levels of stress hormones and decreased secretion of Th1 cytokines
Authors: Cohen Miri , Klein Ehud , Kuten Abraham , Fried Geta , Zinder Oren , Pollack Shimon
Published: September 2002

DBCP who are aware of their increased risk of developing breast cancer may suffer from high emotional distress. Chronic stress may interfere with NCA and low NCA is associated with increased cancer risk. We studied 80 DBCP and 47 age‐ and education‐matched healthy females (controls). Heparinized venous blood (30 ml) was drawn from all subjects between 8 and 9 A.M., and each participant answered a set of psychologic questionnaires. In addition, the first‐morning urine sample was collected. DBCP scored significantly higher in emotional distress compared to controls. Levels of stress hormones in DBCP were higher and in vitro secretion of IL‐2, IL‐12 and IFN‐γ lower compared to controls. NCA against NK‐resistant (MCF‐7, COLO‐205, U937) and NK‐sensitive (K562) cell lines was significantly lower in DBCP and much less augmented by in vitro preincubation with IL‐2 or IL‐12 compared to controls. NCA and in vitro Th1 cytokine secretion were inversely correlated with the degree of emotional distress and the level of stress hormones in blood or urine. High emotional distress and elevated levels of stress hormones are associated with impaired immune surveillance functions in DBCP. This may contribute to the increased risk of DBCP to develop breast cancer. An interventional trial to enhance coping and reduce stress levels may help to decrease the risk for breast cancer onset in DBCP. © 2002 Wiley‐Liss, Inc.
Inhibitory effects of the standardized extract (DA‐9601) of Artemisia asiatica Nakai on phorbol ester–induced ornithine decarboxylase activity, papilloma formation, cyclooxygenase‐2 expression, inducible nitric oxide synthase expression and nuclear transcription factor κB activation in mouse skin
Authors: Seo Hyo‐Joung , Park Kwang‐Kyun , Han Seong Su , Chung Won‐Yoon , Son Mi‐Won , Kim Won‐Bae , Surh Young‐Joon
Published: September 2002

Artemisia asiatica Nakai has been used in traditional Asian medicine for the treatment of inflammatory and other disorders. Previous studies have revealed that the formulated ethanol extract (DA‐9601) of A. asiatica has pronounced antioxidative and antiinflammatory activities and exhibits cytoprotective effects against experimentally induced gastrointestinal, hepatic and pancreatic damage. In the present study, we assessed the inhibitory effect of DA‐9601 on tumor promotion, which is closely linked to inflammatory tissue damage. As an initial approach to evaluating the possible antitumor‐promoting potential of DA‐9601, its effects on TPA‐induced ear edema were examined in female ICR mice. Pretreatment of the inner surface of the mouse ear with DA‐9601 30 min prior to topical application of TPA inhibited ear edema at 5 hr. TPA‐stimulated expression of epidermal COX‐2 and iNOS was also mitigated by topical application of the same extract. Moreover, DA‐9601 abrogated the TPA‐mediated activation of NF‐κB/Rel and AP‐1 in mouse epidermis. Suppression of epidermal NF‐κB by DA‐9601 appeared to be mediated in part through inhibition of IκBα degradation, thereby blocking the nuclear translocation of p65, the functional subunit of NF‐κB. DA‐9601 also significantly suppressed TPA‐induced ODC activity and papilloma formation in mouse skin. Taken together, these findings suggest that DA‐9601 derived from A. asiatica possesses potential chemopreventive activities. © 2002 Wiley‐Liss, Inc.
Expression of maspin predicts poor prognosis in breast‐cancer patients
Authors: Umekita Yoshihisa , Ohi Yasuyo , Sagara Yoshiatsu , Yoshida Hiroki
Published: September 2002

The tumor suppressor genemaspinhas been reported to inhibit the invasiveness and motility of breast cancer cells. It has been reported that maspin is expressed in normal human mammary epithelial cells but is downregulated during cancer progression, and that p53 could induce maspin expression by transcriptional activation. However, to date, the clinical significance of maspin expression and its correlation with p53 protein expression in human breast cancer patients have not been elucidated. One hundred and sixty‐eight female patients diagnosed with invasive ductal carcinoma, who had undergone a mastectomy (154 patients) or breast‐conserving surgery (14 patients), were followed up for 15–119 months (median: 87 months) postoperatively. Immunoreactivity for maspin and p53 antibodies with paraffin‐embedded carcinoma tissue was investigated using labeled streptavidin‐biotin methods. Tumors with more than 20% of positive cells were considered positive for the expression of maspin. The expression of maspin in carcinoma cells was found in 27.4% (46 of 168) and significantly correlated with larger tumor size (p= 0.008), higher histologic grade (p= 0.0001) and positive p53 status (p= 0.003). A significant inverse relationship was observed between the expression of maspin and estrogen receptor (p= 0.0004) or progesterone receptor status (p= 0.02). Univariate analysis by log‐rank test revealed a significant association between the expression of maspin and shorter relapse‐free survival (p< 0.0001) and overall survival (p< 0.0001). According to Cox's multivariate analysis, the expression of maspin had the most significant effect in relapse‐free survival (p< 0.0001) and overall survival (p< 0.0001) followed by lymph node status. In turn, the expression of maspin in 58 cases of ductal carcinomain situwere also investigated to explore whether the downregulation of maspin through cancer progression are true or not. However, there were no positive cases in our series. These results seem to be contrary to previous reports defining maspin as a tumor suppressor gene. Although more precise characterization of the maspin expression, especially gene analysis is essential, the present investigation suggests that the expression of maspin is not downregulated through malignant progression and that the immunohistochemic detection of maspin in carcinoma cells may be helpful for selecting the group of breast cancer patients with an aggressive phenotype. © 2002 Wiley‐Liss, Inc.
Spontaneously formed tumorigenic hybrids of Meth A sarcoma and macrophages grow faster and are better vascularized than the parental tumor
Authors: Busund Lill‐Tove R. , Killie Mette K. , Bartnes Kristian , Seljelid Rolf
Published: September 2002

Macrophages and Meth A sarcoma cells spontaneously fuse and give rise to tumorigenic hybrid cell lines with a mixed phenotype. We report here that the hybrid tumors grow faster and have a strikingly better developed vasculature than the parent sarcoma. Thus, electron microscopy and immunohistochemical analysis revealed that in the most active areas of neovascularization, the tumors that emerged from inocula of monoclonal hybrid cell populations had a microvessel density nearly twice that of Meth A tumors after 1 week of growth. Moreover, the proportion of vessels associated with pericytes, detected by staining for smooth muscle α‐actin, was 3 times higher in the hybrid tumors, attesting to the more advanced differentiation of their vasculature. The collagenous stroma component was also more extensive in the hybrid tumors. Concentration of the angiogenic proteins vascular endothelial growth factor (VEGF) and transforming growth factor‐β (TGF‐β) were significantly higher in supernatants of hybrid cell cultures compared with Meth A cultures. These observations indicate that the growth advantage of the hybrid tumors over the parental sarcoma is due to a higher angiogenic capacity. Because the malignant features of many tumors correlate with angiogenesis and because macrophages are known to be major producers of angiogenic factors, our data open the possibility that the intense neovascularization of highly aggressive cancers in some cases reflects the acquisition of macrophage traits by heterotypic cell fusion. © 2002 Wiley‐Liss, Inc.
Overexpression of Bcl‐2 in squamous cell carcinoma of the larynx: A marker of radioresistance
Authors: Condon Luke T. , Ashman James N.E. , Ell Stephen R. , Stafford Nicholas D. , Greenman John , Cawkwell Lynn
Published: September 2002

Squamous cell carcinoma of the larynx can be treated using radiotherapy or surgery, either alone or in combination. Radiotherapy is preferred for early‐stage tumours, as it spares the larynx and therefore preserves speech and swallowing. Unfortunately, approximately 15% of tumours treated this way will prove to be radioresistant, as manifest by tumour recurrence within the original radiotherapy field over the ensuing 12 months. By causing extensive DNA damage, radiotherapy aims to induce apoptosis and tumour regression. Our hypothesis was that defects in the mechanisms that recognise DNA damage, induce cell cycle arrest or control apoptosis, either alone or in combination, may be responsible for radioresistance. We therefore undertook an immunohistochemic analysis of pretreatment biopsies of radioresistant (n = 8) and radiosensitive (n = 13) laryngeal tumours. To minimise the impact of confounding factors, strict inclusion criteria were observed; all tumours were of the glottic subsite and all recurrences developed within 12 months of radiotherapy at the site of the original tumour. The expression of key proteins involved in DNA damage recognition (p53), cell cycle arrest (ATM, p16 and p21/WAF1) and apoptosis (Bcl‐2 and BAX) were studied. Ki‐67 was also assessed as a marker of cell proliferation to exclude low mitotic rate as a cause of radioresistance. A statistically significant correlation was observed between overexpression of Bcl‐2 and radioresistance (p = 0.003, Fisher's exact test). We hypothesise that overexpression of the anti‐apoptotic protein Bcl‐2 allows tumour cells with extensive radiation‐induced DNA damage to continue proliferating; the absence of an appropriate apoptotic response manifests clinically as radioresistance. © 2002 Wiley‐Liss, Inc.
Prevalence of human papillomavirus in cervical cancer: A multicenter study in China
Authors: Lo Keith W.K. , Wong Y.F. , Chan May K.M. , Li James C.B. , Poon J.S. , Wang Vivian W. , Zhu S.N. , Zhang T.M. , He Z.G. , Wu Q.L. , Li G.D. , Tam John S.L. , Kahn T. , Lam P. , Cheung T.H. , Chung Tony K.H.
Published: September 2002

A large‐scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV‐16 was present in 79.6%, HPV‐18 in 7.5%, HPV‐52 in 2.6% and HPV‐58 in 3.8% of all HPV‐positive specimens. The prevalences of HPV‐16 and HPV‐18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV‐16 and a higher HPV‐18 proportion compared with the other regions. HPV‐16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV‐18 infection was significantly higher in AC than in SCC. © 2002 Wiley‐Liss, Inc.
Inhibitory effect of a selective cyclooxygenase‐2 inhibitor on liver metastasis of colon cancer
Authors: Nagatsuka Isao , Yamada Nobuya , Shimizu Sadatoshi , Ohira Masaichi , Nishino Hiroji , Seki Shuichi , Hirakawa Kosei
Published: September 2002

COX‐2 overexpression is recognized in various cancers, but the role of COX‐2 in the progression of cancer, including the liver metastasis of colon cancer, is not clearly understood. We examined the role of COX‐2 in the mechanism of liver metastasis of colon cancer, using a highly metastasizable colon carcinoma cell line, LM‐H3. A COX‐2 inhibitor, JTE‐522, inhibited cell proliferation and invasion of LM‐H3 in vitro and clearly reduced the number of metastatic nodules on the surface of nude mouse livers in vivo. We also examined the effects of JTE‐522 on the production of growth factors and MMPs through the use of ELISA and gelatin zymography, respectively. JTE‐522 downregulated PDGF production by LM‐H3 but had no influence on VEGF production. JTE‐522 also inhibited MMP‐2 secretion by LM‐H3. JTE‐522 downregulated PGE2 production, but the associated changes in PGE2 did not affect PDGF and VEGF production by LM‐H3. We conclude that JTE‐522 downregulated the cell proliferation and invasive potential of LM‐H3 by reducing the production of PDGF and MMP‐2 and hypothesize that these inhibitory effects on the production of PDGF and MMP‐2 can lead to inhibition of liver metastasis of colon cancer. These data indicate that the COX‐2 inhibitor JTE‐522 has a high potential for use as a clinical agent for the treatment of liver metastasis of colon cancer. © 2002 Wiley‐Liss, Inc.
IFN‐γupregulates apoptosis‐related molecules and enhances Fas‐mediated apoptosis in human cholangiocarcinoma
Authors: Ahn Eun‐Young , Pan George , Vickers Selwyn M. , McDonald Jay M.
Published: September 2002

Human cholangiocarcinoma is a malignancy with no effective therapy and a poor prognosis. Previously, we demonstrated that cultured human cholangiocarcinoma cell lines heterogeneously express Fas on their surface, resulting in 2 subpopulations, Fas‐high and Fas‐low cells. Fas‐low cells are resistant to apoptosis induced by Fas antibody and the calmodulin antagonists tamoxifen and trifluoperazine and are tumorigenic in nude mice (Pan et al., Am J Pathol 1999;155:193–203). Here, we show that IFN‐γ enhances apoptosis in both Fas‐high and Fas‐low cells. IFN‐γ upregulates many apoptosis‐related molecules, including Fas, caspase‐3, caspase‐4, caspase‐7, caspase‐8 and Bak, in both cell lines. Pretreatment with IFN‐γ facilitated Fas‐mediated caspase cleavage, cytochrome c release and Bax translocation. The ability of IFN‐γ to inhibit tumorigenesis of Fas‐low cells was demonstrated in nude mice. Intratumoral injection of IFN‐γ decreased tumor volumes by 78%. These findings indicate that IFN‐γ modulates the apoptotic pathway by upregulating apoptosis‐related genes. This renders tumorigenic Fas‐low cholangiocarcinoma cells nontumorigenic and sensitive to Fas apoptosis, thus representing a possible therapeutic modality. © 2002 Wiley‐Liss, Inc.
Detection of free‐circulating tumor‐associated DNA in plasma of colorectal cancer patients and its association with prognosis
Authors: Lecomte Thierry , Berger Anne , Zinzindohoué Franck , Micard Stéphanie , Landi Bruno , Blons Hélène , Beaune Philippe , Cugnenc Paul‐Henri , Laurent‐Puig Pierre
Published: September 2002

Tumor cells are characterized by specific genetic alterations. When such genetic alterations are identified in body fluid including plasma, regardless of the presence of detectable tumor cells, it shows the existence of free‐circulating tumor‐associated DNA. The objective of our study was to assess the prognostic value of free‐circulating tumor‐associated DNA in colorectal cancer patients' plasma. The first step of our work was to find common genetic alterations in tumors that would subsequently be used for plasma DNA screening. We focused on KRAS2 mutations in codons 12 and 13 by the mutant allele‐specific amplification (MASA) method and p16 hypermethylation by the methylation‐specific polymerase chain reaction (MSP) method. Patients with a tumor presenting either alteration were selected for plasma screening; 58 tumors were analyzed forKRAS2mutations and tested forp16gene promoter methylation. Survival and recurrence rates were assessed in patients with and without free‐circulating tumor‐associated DNA alterations in plasma. Of the 58 tumors analyzed, 39 (67%) demonstrated either one or both of the studied genetic alterations. Twenty‐two (38%) were mutated atKRAS2, and an identical alteration was detected in 10 (45%) of the 22 corresponding plasma samples. Thirty‐one (53%) hadp16gene promoter hypermethylation that could also be detected in the plasma in 21 cases (68%). Among the 39 patients who had one or the other alteration in tumor DNA, 37 had at least one reliable plasma test. In 26 (70%) of the 37 patients, free‐circulating tumor‐associated DNA was detected in plasma. The 2‐year overall survival rate was 48% in the group where free‐circulating tumor‐associated DNA was detected in plasma and 100% in the one where free‐circulating tumor‐associated DNA was not detected in plasma (p< 0.03). Among these 37 patients, 25 patients had a stage I, II or III disease. In this subgroup of patients, the 2‐year recurrence‐free survival rate for the 17 patients with free‐circulating tumor‐associated DNA detected in plasma was 66%, compared to 100% for the 8 patients without free‐circulating tumor‐associated DNA detected in plasma (p= 0.044). The presence of free‐circulating tumor‐associated DNA in plasma seems to be a relevant prognostic marker for patients with colorectal cancer and may be used to identify patients with a high risk of recurrence. © 2002 Wiley‐Liss, Inc.
Professional and managerial migration from core to periphery: the case of English migration to Scottish cities
Authors: Findlay A. M. , Stockdale A. , Stewart E.
Published: September 2002

The population of English‐born persons living in Scotland has risen rapidly since 1971. The dynamics of the group are theorised in this paper relative to the escalator region hypothesis, in terms of the role of professional and managerial staff linking global cities with lower‐order urban centres within their hinterland. A hierarchical log‐linear modelling approach is taken in explaining the highly structured geography of English migration to Scotland's four largest urban centres. Links between place of birth, recent mobility, social class and car ownership are explored. It is argued that service class migration by the English to Scottish cities is representative of a much wider process found in other countries where economic and political integration has stimulated parallel types of skilled migration from core to peripheral urban locations. Copyright © 2002 John Wiley & Sons, Ltd.
Assessing the opinions of users of water projects
Authors: Abernethy Charles L. , Jinapala K. , Makin I.W.
Published: September 2002

A methodology is described for measuring the opinions of rural people who are affected by water‐related development and conservation projects. The method is illustrated by results from three applications of the methodology at sites in Sri Lanka. Aspects of the technique, the preparation of questionnaires, and the analysis of findings, are discussed. Copyright © 2001 John Wiley & Sons, Ltd.