bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population
Authors: Liang Gang , Xing Deyin , Miao Xiaoping , Tan Wen , Yu Chunyuan , Lu Wenfu , Lin Dongxin 
Published: May 2003

AbstractVariation in DNA repair capacity, which is believed to be largely determined by genetic traits, is linked to risk of certain cancers. The Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may alter DNA repair capacity. We thus examined the hypothesis that these 2 XPD polymorphisms are associated with risk of lung cancer via a large hospital‐based, case‐control study among Chinese. The study subjects consisted of 1,006 patients with primary lung cancer and 1,020 age‐ and sex‐matched population controls. XPD genotypes were determined using PCR‐RFLP techniques, and the associations between genotypes and risk of lung cancer were estimated by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated by unconditional logistic regression. Subjects homozygous for the 312Asn/Asn genotype had an increased risk of lung cancer (adjusted OR = 10.33, 95% CI = 1.29–82.50) compared with subjects homozygous for the 312Asp/Asp genotype. The 751Gln/Gln genotype was also associated with increased risk for the cancer compared with the 751Lys/Lys genotype (adjusted OR = 2.71, 95% CI = 1.01–7.24). Stratification analysis revealed that the increased risk was mainly confined to lung squamous cell carcinoma, with the ORs being 20.50 (95% CI = 2.25–179.05) for the 312Asn/Asn genotype and 4.24 (95% CI = 1.34–13.38) for the 751Gln/Gln genotype, respectively. Haplotype analysis with the 2 polymorphisms suggested these polymorphisms might be in linkage disequilibrium with a different causative locus or act together with other functional variants in or close to the XPD locus. © 2003 Wiley‐Liss, Inc.
Clinical significance of detecting elevated serum DcR3/TR6/M68 in malignant tumor patients
Authors: Wu Yulian , Han Bing , Sheng Hongwei , Lin Min , Moore Paul A. , Zhang Jun , Wu Jiangping 
Published: May 2003

AbstractTR6/DcR3/M68 is a soluble receptor that belongs to the TNF receptor family. It is expressed in malignant cells of several tumor types and has been postulated to help tumor cells to gain survival advantage by inhibiting apoptosis and by interfering with immune surveillance. In our study, we assessed for the first time serum TR6 in tumor patients to explore its diagnostic and prognostic value. We examined serum TR6 levels with ELISA in 146 tumor patients, 19 patients with acute infection, 5 patients with liver cirrhosis and 29 healthy individuals. TR6 expression in tumor mass was studied with immunohistochemistry. TR6 gene copy number in tumor tissues was evaluated by real time PCR. Ninety‐seven point nine percent (47 of 48 cases) of healthy individuals and patients with acute infection were serum TR6‐negative. In contrast, 56.2% (82 of 146 cases) of the tumor patients were serum TR6‐positive. Almost all serum TR6‐positive individuals (98.8%, 82 out of 83 cases) had malignancy, excluding the cases of liver cirrhosis. In gastric carcinomas, serum TR6 levels were closely correlated with tumor differentiation status and TNM classification. Tumor mass was the source of serum TR6 because its levels decreased drastically after curative tumor resection. TR6 gene amplification occurred in about half of liver carcinomas, but not in gastric or pancreatic carcinomas, indicating plural mechanisms of TR6 upregulation. Our study demonstrated that serum TR6 should be considered as a novel parameter for the diagnosis, treatment and prognosis of malignancies. © 2003 Wiley‐Liss, Inc.
Natural killer (NK) cell function is a strong prognostic factor in colorectal carcinoma patients treated with the monoclonal antibody 17‐1A
Authors: Liljefors Maria , Nilsson Bo , Hjelm Skog Anna‐Lena , Ragnhammar Peter , Mellstedt Håkan , Frödin Jan‐Erik 
Published: May 2003

AbstractTumor cells might be susceptible to different effector functions of the immune system. This cytotoxic capacity has been utilized to analyze the prognostic significance of peripheral blood mononuclear cells (PBMC) in patients with metastatic colorectal carcinoma (CRC) treated with the monoclonal antibody (MAb)17‐1A. Such analysis might form the basis for future patient selection and may lead to improvements in therapeutic strategies. Between 1986 and 1998, 73 patients were treated with regimens containing MAb17‐1A. Prior to therapy, the lytic capability of PBMC was assayed against: K562 (4 hr assay), the CRC cell line SW948 (4 hr and 18 hr assays) and antibody‐dependent cellular cytotoxicity (ADCC, 18 hr assay). Since the study was performed over 13 years, the assays were checked for time‐related bias. Reproducibility over time was satisfactory. Patients exhibited a significantly higher cytotoxic capability in all 4 assays compared to healthy control donors. No correlation to clinical outcome was noted for 18 hr ADCC and 18 hr spontaneous cytotoxicity. Pretreatment natural killer (NK) cell cytotoxicity (K562) was significantly related to overall survival (OS), progression‐free survival (PFS), and response rate. OS for patients with high and low NK cell cytotoxicity was 71 vs. 30 weeks, respectively (p = 0.007). NK cell cytotoxicity (K562) was an independent prognostic factor for OS (p = 0.016). Pretreatment NK cell activity is a strong prognostic factor for patients with metastatic CRC receiving MAb17‐1A therapy and is a predictor for OS, PFS and response. These results should be considered when designing antibody‐based therapeutic protocols. © 2003 Wiley‐Liss, Inc.
Development of resistance to a trinuclear platinum complex in ovarian carcinoma cells
Authors: Perego Paola , Gatti Laura , Righetti Sabina C. , Beretta Giovanni L. , Carenini Nives , Corna Elisabetta , Bo Laura Dal , Tinelli Stella , Colangelo Donato , Leone Roberto , Apostoli Piero , Lombardi Luciano , Beggiolin Gino , Piazzoni Laura , Zunino Franco 
Published: May 2003

AbstractBBR3464 is a trinuclear platinum complex that exhibits a potent cytotoxicity and efficacy against cisplatin‐resistant tumors. To better understand the determinants of cellular resistance to BBR3464, we selected a resistant ovarian carcinoma cell line after exposure to the complex. The resistant cells (A2780/BBR3464) exhibited a high level of resistance to the selecting agent, but a marginal cross‐resistance to cisplatin. Although cellular accumulation of BBR3464 was similar in parental and in resistant cells, DNA platination was decreased in A2780/BBR3464 cells, suggesting a reduced drug accessibility to DNA. This behavior reflected a partial drug inactivation at cytoplasmic level, as a consequence of increased levels of nucleophilic molecules including metallothioneins and human neurofilament low, but not glutathione. A2780/BBR3464 cells also exhibited a reduced susceptibility to apoptosis, which was consistent with reduced expression of Bax, and an alteration of DNA mismatch repair system, as reflected by lack of expression of MLH1 and PMS2, which could impair the recognition/repair of DNA lesions. Whereas both platinum drugs induced G2/M arrest in the parental cells, BBR3464, but not cisplatin, caused a late G1 arrest of resistant cells. Cisplatin induced an appreciable increase of p21WAF1 levels in both models, in contrast to BBR3464 that produced a substantial upregulation of p21WAF1 only in parental cells. An inverse relationship with p21WAF1 modulation was found for CHK1 in parental cells treated with both agents and in resistant cells treated with cisplatin. This pattern of response is consistent with a regulatory loop involving p53 and p21WAF1 at G2 checkpoint. In contrast, no modulation of CHK1 was found in A2780/BBR3464 treated with the triplatinum compound. These findings, indicating a different activation of regulatory pathways at DNA damage checkpoints in response to cisplatin and BBR3464, support an altered ability of resistant cells to recognize or tolerate sublethal lesions induced by BBR3464. © 2003 Wiley‐Liss, Inc.
Meta‐analysis of social inequality and the risk of cervical cancer
Authors: Parikh Seema , Brennan Paul , Boffetta Paolo 
Published: May 2003

AbstractPrevious studies of the relationship between socio‐economic status and cervical cancer have been mainly based on record linkage of routine data, such as cancer registry incidence rates and regional measures of social class based on census data. These routine data are liable to substantial misclassification with respect to socio‐economic status. Previous reports are also primarily from developed countries, whereas the major burden of cervical cancer is in developing countries. We have therefore pooled the data from previously reported case‐control studies of cervical cancer or dysplasia, which contain individual‐level information on socio‐economic characteristics to investigate the relationship between cervical cancer, social class, stage of disease, geographical region, age and histological type. Based on 57 studies, we found an increased risk of approximately 100% between high and low social class categories for the development of invasive cervical cancer, and an increased risk of approximately 60% for dysplasia, including carcinoma in situ. Although the difference was observed in all countries, it was stronger in low/middle income countries and in North America than in Europe. No clear differences were observed between squamous cell carcinoma and adenocarcinoma, or between younger and older women. These results indicate that both cervical infection with human papillomavirus, which is linked to both female and male sexual behaviour, and access to adequate cervical cancer screening programmes are likely to be important in explaining the large cervical cancer incidence rates observed in different socio‐economic groups, and that the importance of these factors may vary between different geographical regions. © 2003 Wiley‐Liss, Inc.
Activation of 3‐nitrobenzanthrone and its metabolites by human acetyltransferases, sulfotransferases and cytochrome P450 expressed in Chinese hamster V79 cells
Authors: Arlt Volker M. , Glatt Hansruedi , Muckel Eva , Pabel Ulrike , Sorg Bernd L. , Seidel Albrecht , Frank Heinz , Schmeiser Heinz H. , Phillips David H. 
Published: May 2003

Abstract3‐Nitrobenzanthrone (3‐NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and ambient air pollution. 3‐Aminobenzanthrone (3‐ABA), 3‐acetylaminobenzanthrone (3‐Ac‐ABA) and N‐acetyl‐N‐hydroxy‐3‐aminobenzanthrone (N‐Ac‐N‐OH‐ABA) have been identified as 3‐NBA metabolites. Recently we found that 3‐NBA and its metabolites (3‐ABA, 3‐Ac‐ABA and N‐Ac‐N‐OH‐ABA) form the same DNA adducts in vivo in rats. In order to investigate whether human cytochrome P450 (CYP) enzymes (i.e., CYP1A2), human N,O‐acetyltransferases (NATs) and sulfotransferases (SULTs) contribute to the metabolic activation of 3‐NBA and its metabolites, we developed a panel of Chinese hamster V79MZ‐h1A2 derived cell lines expressing human CYP1A2 in conjunction with human NAT1, NAT2, SULT1A1 or SULT1A2, respectively. Cells were treated with 0.01, 0.1 or 1 μM 3‐NBA, or its metabolites (3‐ABA, 3‐Ac‐ABA and N‐Ac‐N‐OH‐ABA). Using both enrichment versions of the 32P‐postlabeling assay, nuclease P1 digestion and butanol extraction, essentially 4 major and 2 minor DNA adducts were detected in the appropriate cell lines with all 4 compounds. The major ones were identical to those detected in rat tissue; the adducts lack an N‐acetyl group. Human CYP1A2 was required for the metabolic activation of 3‐ABA and 3‐Ac‐ABA (probably via N‐oxidation) and enhanced the activity of 3‐NBA (probably via nitroreduction). The lack of acetylated adducts suggests N‐deacetylation of 3‐Ac‐ABA and N‐Ac‐N‐OH‐ABA. Thus, N‐hydroxy‐3‐aminobenzanthrone (N‐OH‐ABA) appears to be a common intermediate for the formation of the electrophilic arylnitrenium ions capable of reacting with DNA. Human NAT1 and NAT2 as well as human SULT1A1 and SULT1A2 strongly contributed to the high genotoxicity of 3‐NBA and its metabolites. Moreover, N,O‐acetyltransfer reactions catalyzed by human NATs leading to the corresponding N‐acetoxyester may be important in the bioactivation of N‐Ac‐N‐OH‐ABA. As human exposure to 3‐NBA is likely to occur primarily via the respiratory tract, expression of CYPs, NATs and SULTs in respiratory tissues may contribute significantly and specifically to the metabolic activation of 3‐NBA and its metabolites. Consequently, polymorphisms in these genes could be important determinants of lung cancer risk from 3‐NBA. © 2003 Wiley‐Liss, Inc.
Interspecies contamination of the KM3 cell line: Implications for CD63 function in melanoma metastasis
Authors: Moseley Gregory W. , Elliott Jill , Wright Mark D. , Partridge Lynda J. , Monk Peter N. 
Published: May 2003

AbstractCD63 is a member of the tetraspanin superfamily of membrane glycoproteins that has been hypothesised to provide a structural network in the organisation of large multimolecular microdomains at cell membranes. Detailed analyses of the role of CD63 in these complexes through mutagenic studies have been limited, however, by the ubiquitous cellular expression of CD63in vivoandin vitro. In an attempt to define CD63‐null cell lines, we have analysed the expression of CD63 and other tetraspanins on a panel of human cancer cell lines. Similar expression patterns were seen between cell lines from melanomas, breast cancers and prostate cancers. The melanoma cell line KM3, however, described previously as a CD63‐null human cell line, was found to express none of the 7 human tetraspanins tested. KM3 was identified definitively as a rat cell line by analysis of karyotype and antigen expression. Notably, KM3 was found to express the rat homologue of CD63. Conclusions concerning the function of human CD63 drawn from studies using KM3 cells therefore require re‐evaluation as does the frequently cited hypothesis that CD63 expression is linked to melanoma progression. As KM3 is the only cell line thus far identified as CD63 negative, these results highlight the necessity for the production of a CD63 null system. © 2003 Wiley‐Liss, Inc.
Telomerase activity in high‐grade cervical lesions is associated with allelic imbalance at 6Q14–22
Authors: van Duin Mark , Steenbergen Renske D.M. , de Wilde Jillian , Helmerhorst Theo J.M. , Verheijen René H.M. , Risse Elle K.J. , Meijer Chris J.L.M. , Snijders Peter J.F. 
Published: May 2003

AbstractOur study attempts to establish the relationship between telomerase activity and allelic imbalance (AI) on chromosomes 3p and 6 in high‐risk HPV‐containing cervical lesions. These chromosomes were implicated previously in telomerase regulation in HPV containing immortalized cells and cervical cancer cells. Allelotyping and telomerase analysis were carried out on 28 high‐grade cervical lesions (CIN III: n = 20; cervical carcinomas: n = 8), using 23 microsatellite markers on 3p, 6p and 6q. Clear telomerase activity was found in 17 of 28 lesions (61%). Allelic imbalance frequency at 6q14–22 was significantly higher in lesions with detectable telomerase activity, compared to lesions without telomerase activity (p = 0.02). No association was found between telomerase activity and AI at any of the remaining regions studied on 3p and chromosome 6. In addition, in telomerase positive passages of the HPV 16 immortalized cell line FK16A, shown recently to be responsive to chromosome 6 mediated telomerase repression, AI was found in the overlapping region of 6q14–27. These data suggest that 6q14–22 may contain 1 or more genes involved in telomerase deregulation and immortalization during cervical carcinogenesis. © 2003 Wiley‐Liss, Inc.
Repression of Smad‐dependent transforming growth factor‐β signaling by Epstein‐Barr virus latent membrane protein 1 through nuclear factor‐κB
Authors: Mori Naoki , Morishita Mariko , Tsukazaki Tomoo , Yamamoto Naoki 
Published: May 2003

AbstractEBV‐encoded LMP‐1 is absolutely required for EBV transformation of cells. Previous studies showed that LMP‐1 is responsible for mediating resistance to the anti‐proliferative effects of TGF‐β that characterizes EBV‐transformed cells. To clarify the mechanisms of resistance to TGF‐β by LMP‐1, we examined the effect of expression of LMP‐1 on the activity of TGF‐β‐responsive promoters. Interestingly, LMP‐1 inhibited TGF‐β‐responsive promoters activity despite lack of direct interaction of LMP‐1 and Smad proteins, intracellular signaling molecules in the TGF‐β signal transduction pathway. Although TGF‐β treatment increased the expression of p15, TGF‐β‐induced gene, this effect was counteracted by expression of LMP‐1. The repressive effect was mapped to the NF‐κB activation domains in the cytoplasmic carboxyl terminus of LMP‐1. Furthermore, LMP‐1‐mediated inhibition of TGF‐β‐responsive promoter was markedly restored after inhibition of NF‐κB activity. LMP‐1 failed to affect receptor‐dependent formation of heteromers containing Smad proteins as well as the DNA‐binding activity of Smad proteins. Overexpression of the transcriptional coactivator CBP and p300 abrogated the inhibitory effect of LMP‐1 on the TGF‐β‐responsive promoter. Our results suggest that LMP‐1 represses the TGF‐β signaling through the NF‐κB signaling pathway at transcriptional level by competing for a limited pool of transcriptional coactivators. These results enhance our understanding of the molecular mechanisms of viral pathogenesis in EBV‐associated malignancies. © 2003 Wiley‐Liss, Inc.
Antiestrogens are pro‐apoptotic in normal human breast epithelial cells
Authors: Somaï Sonia , Chaouat Marc , Jacob Denis , Perrot Jean‐Yves , Rostène William , Forgez Patricia , Gompel Anne 
Published: May 2003

AbstractEstrogens promote cell proliferation in normal and transformed mammary epithelial cells by inducing expression of hormone‐responsive genes involved in the cell cycle. The action of antiestrogens is therefore central in regard to their potent inhibitory effects on estrogen‐induced cell growth. We used normal human epithelial breast cells from primary cultures (HBE cells) to study hormonal (estrogen and antiestrogen) regulation on 3 key proteins involved in the apoptotic process: Bcl‐2, p53 and caspase‐3. The mammary adenocarcinoma cell line, MCF‐7, was also used to study the molecular regulation of Bcl‐2. In both HBE and MCF‐7 cells, we found that estradiol (E2) induced an increase in Bcl‐2 mRNA levels. This effect was counteracted in the presence of a pure antiestrogen, ICI 182780 (ICI). Alone, ICI did not modify either the Bcl‐2 protein or mRNA levels in HBE cells, whereas in MCF‐7, a strong downregulation of Bcl‐2 mRNA was observed. In parallel, in HBE cells, we observed that E2 caused a decrease in p53 and caspase‐3 protein levels, whereas ICI alone increased p53 and caspase‐3 protein levels. The ICI effects on p53 and caspase‐3 were partially counteracted by E2. Under the same experimental conditions, ICI exerts a potent pro‐apoptotic effect, which was not counteracted by E2. In contrast, 4‐hydroxytamoxifen was slightly weaker as a pro‐apoptotic agent in HBE cells and its effects were reversed by E2. We demonstrate that in HBE cells, ICI reverses the anti‐apoptotic action of E2 and alone acts as a highly potent pro‐apoptotic molecule. These results provide new insight into treatment for breast cancer prevention. © 2003 Wiley‐Liss, Inc.
Socioeconomic factors in cancer in Sweden
Authors: Hemminki Kari , Zhang Hong , Czene Kamila 
Published: May 2003

AbstractIt is well known that certain cancers have shown clustering in socioeconomic groups, but limited data are available on recent results and time trends in such clustering. We determined standardized incidence ratios (SIR) for cancer, adjusted for age, period, region, parity and age at first childbirth among men and women in 6 socioeconomic groups based on the Swedish Family‐Cancer Database. Persons had to be identified with the same socioeconomic status in the census of years 1960 and 1970, or of years 1960, 1970 and 1980; the comparison group was all people according to the same censuses. Cancers were followed from years 1970 to 1998 or from 1980 to 1998. Both increased and decreased SIRs were found, and a consistent pattern emerged, although the overall SIRs for cancer did not differ much, the lowest being for farmers (0.85) and the highest for professional men (1.07) and women (1.11). At individual sites, manual workers were at risk of tobacco‐, alcohol‐ and occupation‐ and human papilloma virus‐related cancers and at a decreased risk at most other cancers. Manual workers and farmers showed an excess of stomach cancer; professionals had an excess of melanoma and squamous cell skin cancer. Male and female SIRs correlated highly for manual and blue‐collar workers and for professionals. The overall population‐attributable fraction for selected sites was 16.7% for men and 10.9% for women and it was highest, over 50%, for lung cancer in both genders. © 2003 Wiley‐Liss, Inc.
Familial invasive and borderline ovarian tumors by proband status, age and histology
Authors: Hemminki Kari , Granström Charlotta 
Published: May 2003

AbstractAge‐specific familial risks in ovarian cancer have not been assessed by histologic types of medically verified cancers. We used the nationwide Swedish Family‐Cancer Database on 10.2 million individuals and 19,175 invasive and 3,436 borderline ovarian cancers to calculate, by affected family members, standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for familial ovarian cancer in 0–66 year old daughters. SIRs for all invasive ovarian cancer were 2.68 (95% CI 2.22–3.21) by ovarian cancer in mother, 2.94 (1.40–5.94) by an affected sister and 24.03 (6.12–74.46) by both an affected mother and sister. The population‐attributable fraction from mothers was 2.52%. Seropapillary cystadenocarcinoma showed the highest familial risk, but the effect of histopathol subtype could not be fully assessed because of lack of data in probands. Age‐specific data showed some early‐onset components and an unusual maximal incidence in the 40s. A comparison to an earlier study on BRCA1/2 mutation analysis and relative risks of ovarian and breast cancer suggests that these mutations could account for 26% of the familial aggregation of ovarian cancer. Histopathology and age of onset appear to be important attributes of familial ovarian cancer, suggesting that further gene identification efforts should target a specific histopathology in early‐onset patients. © 2003 Wiley‐Liss, Inc.
Involvement of PKC βII in anti‐proliferating action of a new antitumor compound gnidimacrin
Authors: Yoshida Mitsuzi , Heike Yuji , Ohno Shigeo , Ikekawa Tetsuro , Wakasugi Hiro 
Published: May 2003

AbstractDaphnane‐type diterpene gnidimacrin (NSC 252940) shows significant antitumor activity against murine tumors and human tumor cell lines. This compound binds to and directly activates protein kinase C (PKC), arresting the cell cycle at the G1 phase through inhibition of cdk2 activity in human K562 leukemia cells. In our study, we examined whether cellular PKC is involved in the antiproliferating effect of gnidimacrin. In a 24‐hr exposure of K562 cells to high concentrations of bryostatin 1 (0.11–3.3 μM), both expression of PKC α and PKC βII was downregulated, and thereafter these cells became resistant to gnidimacrin in response to the degree of PKC downregulation. In addition, PKC α and PKC βII genes were transfected to gnidimacrin‐resistant human hepatoma HLE cells that demonstrated positive expression of PKC α and negative expression of PKC βII. PKC βII gene‐transfected cells became sensitive to gnidimacrin in relation to the degree of PKC βII expression. The most sensitive clone to show 0.001 μg/mL (1.2 nM) as IC50 in a continuous 4‐day exposure was obtained. While PKC α gene‐transfected cells exhibited an increase in PKC α expression and became sensitive to gnidimacrin, sensitivity was one‐hundredth of that in PKC βII gene‐transfected cells. These results suggest that PKC, in particular PKC βII, is necessary in the antitumor effect of gnidimacrin. © 2003 Wiley‐Liss, Inc.