bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biodistribution and pharmacokinetics of 125I‐labeled monoclonal antibody M75 specific for carbonic anhydrase IX, an intrinsic marker of hypoxia, in nude mice xenografted with human colorectal carcinoma
Authors: Chrastina Adrián , Závada Jan , Parkkila Seppo , Kaluz Štefan , Kaluzová Milota , Rajčáni Július , Pastorek Jaromír , Pastoreková Silvia 
Published: May 2003

AbstractCarbonic anhydrase IX (CA IX) is frequently expressed in human carcinomas and absent from the corresponding normal tissues. Strong induction by tumor hypoxia predisposes CA IX to serve as a target for cancer diagnostics and therapy. Here we evaluated targeting properties and pharmacokinetics of CA IX‐specific monoclonal antibody (MAb) M75. Binding parameters of 125I‐labeled M75, including equilibrium dissociation constant, hypoxia‐related binding to various cell lines and internalization, were analyzed in vitro. Biodistribution of 125I‐M75 in nude mice bearing HT‐29 human colorectal carcinoma xenografts with hypoxic pattern of CA IX expression was studied by measurements of radioactivity in dissected tissues and macroautoradiography of tissue sections. Pharmacokinetics of intravenously administered 125I‐M75 was described using a 2‐compartment model. Blood clearance showed a distribution phase t1/2(α) = 3.4 hr and an elimination phase t1/2(β) = 55.3 hr postinjection. Despite predominant CA IX localization in less accessible perinecrotic regions, 125I‐M75 exhibited specific accumulation in xenograft, with a mean uptake of 15.3 ± 3.6% of injected dose per gram of tumor tissue at 48 hr postadministration. Specificity of M75 localization was confirmed by low tumor uptake of control antibody. Altogether, our data demonstrate that M75 MAb is a promising tool for selective immunotargeting of hypoxic human tumors that express CA IX. © 2003 Wiley‐Liss, Inc.
Overexpression of RbAp46 facilitates stress‐induced apoptosis and suppresses tumorigenicity of neoplastigenic breast epithelial cells
Authors: Li Guan‐Cheng , Guan Li‐Shuang , Wang Zhao‐Yi 
Published: May 2003

AbstractWe have found previously that the retinoblastoma (Rb) suppressor associated protein 46 (RbAp46) is a gene upregulated by the Wilms' tumor suppressor, WT1, and functions as a potent growth inhibitor. To investigate the effect of RbAp46 overexpression on early development of breast cancer, we established stable cell lines from neoplastigenic breast epithelial cells, MCF10AT3B, a cell line derived from a model of human proliferative disease, to constitutively express exogenous RbAp46. We have found that expression of RbAp46 suppressed colony formation of MCF10AT3B cells in soft‐agar, and inhibited tumor formation of these cells in nude mice. Expression of RbAp46 sensitized MCF10AT3B cells to apoptosis induced by serum deprivation and hydrocortisone withdrawal. Furthermore, we have found that the c‐Jun NH2‐terminal kinase (JNK) pathway and GADD45, a growth arrest‐ and DNA damage‐inducible gene, are constitutively activated in RbAp46‐expressing cells. Our data suggested that high levels of RbAp46 expression inhibit the tumorigenicity of neoplastigenic breast epithelial cells by facilitating JNK‐dependent apoptotic cell death. Our data also suggested that dysregulation of RbAp46 gene may be involved in the early development of breast cancer. © 2003 Wiley‐Liss, Inc.
Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8+ T cells
Authors: Radford Kristen J. , Jackson Andrew M. , Wang Jui‐Ho , Vassaux Georges , Lemoine Nicholas R. 
Published: May 2003

AbstractThe generation of tumour‐specific cytotoxic T‐lymphocyte (CTL) responses is the primary focus in the design of immunotherapeutic cancer vaccines. We have recently demonstrated generation of ovalbumin (OVA)‐specific CTLs and tumour‐protection in a murine tumour model using vaccination with dendritic cells (DCs) pulsed with E. coli expressing listeriolysin O (LLO) and OVA as a model antigen. In this system paraformaldehyde fixation of E. coli/LLO provided an additional safety feature without compromising vaccine efficacy. We therefore reasoned that paraformaldehyde‐fixed recombinant E. coli expressing LLO would be an efficient vehicle for the delivery of human tumour antigens to human DCs. In the present study, we demonstrate that fixed E. coli expressing LLO are taken up efficiently by human monocyte‐derived DCs (MoDCs) with minimal toxicity. As a consequence of the interaction with bacteria, human DCs undergo marked phenotypic and functional maturation. Furthermore, we show that fixed E. coli/LLO expressing the well‐characterised human melanoma antigen, MART1, efficiently deliver the HLA‐A2‐restricted MART127–35 epitope for processing and presentation on human MoDCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy. © 2003 Wiley‐Liss, Inc.
Downregulation of Cap43 gene by von Hippel‐Lindau tumor suppressor protein in human renal cancer cells
Authors: Masuda Katsuaki , Ono Mayumi , Okamoto Masahiro , Morikawa Wataru , Otsubo Michihiro , Migita Toshiro , Tsuneyoshi Masazumi , Okuda Heiwa , Shuin Taro , Naito Seiji , Kuwano Michihiko 
Published: May 2003

AbstractWe previously identified 9 genes (i.e., thymosin β4, secreted protein acidic and rich in cysteine, Cap43, ceruloplasmin, serum amyloid A, heat shock protein 90, LOT1, osteopontin and casein kinase Iγ) that are more highly expressed in cancerous regions than in noncancerous regions in human renal cancers. In our study, we considered the possibility that the von Hippel‐Lindau (VHL) tumor suppressor gene might be able to affect the expression of these 9 genes in renal cancer cells. We first established 2 VHL‐positive cell lines, 786/VHL‐1 and 786/VHL‐2, after the introduction of wild‐type VHL into VHL‐negative renal cancer 786‐O cells. Of these 9 genes, expression of the Cap43 gene was specifically downregulated by VHL. Expression of Cap43 was also much lower in 4 other VHL‐positive renal cancer cell lines than in VHL‐negative 786‐O cells. Cap43 promoter assays with several deletion or mutation constructs demonstrated that the Sp1 site in the element from –286 base pairs (bp) to –62 bp was partly responsible for VHL‐induced suppression of the Cap43 gene. Immunostaining analysis with human specimens of renal cancers demonstrated that the Cap43 protein was expressed in most cancer cells and macrophages. We also observed a marked and specific increase of Cap43 mRNA levels in response to hypoxia or nickel in all VHL‐positive cell lines. Cellular expression of Cap43 mRNA in response to hypoxia or nickel thus is closely associated with VHL gene expression in renal cancer cells. Although the function of the Cap43 protein remains unclear, the expression of Cap43 protein could be a molecular marker closely associated with VHL in renal cancer. © 2003 Wiley‐Liss, Inc.
Growth inhibitory retinoid effects after recruitment of retinoid X receptor β to the retinoic acid receptor β promoter
Authors: Cheung Belamy , Yan Joanne , Smith Stewart A. , Nguyen Tue , Lee Michelle , Kavallaris Maria , Norris Murray D. , Haber Michelle , Marshall Glenn M. 
Published: May 2003

AbstractNuclear retinoid receptors mediate retinoid effects through tissue‐specific, ligand–receptor interactions and subsequent transcriptional regulation of secondary target genes. Retinoic acid receptor beta (RARβ) is itself a retinoid target gene with a retinoic acid response element (βRARE) in the 5′ untranslated region of the RARβ2 gene. Altered transcriptional regulation of RARβ may play a role in human carcinogenesis and the retinoid‐responsiveness of malignant cells. Here we used retinoid X receptor‐specific antibodies in electrophoretic mobility shift assays to show that the retinoid X receptor β (RXRβ) protein was recruited to the βRARE, after retinoid treatment of retinoid‐sensitive neuroblastoma (NB), lung and breast cancer cell lines, but not retinoid‐resistant lung and breast cancer cell lines. RXRβ selectively enhanced retinoid‐induced transcriptional activation of the βRARE. Stable overexpression of RXRα and RXRβ in NB cells resulted in marked growth inhibition and cell death, which increased after retinoid treatment. However, only proteins from the RXRβ transfectants exhibited specific RXRβ binding to the βRARE in vitro and in vivo, enhanced histone acetylation and increased endogenous RARβ expression. These data indicate that recruitment of RXRβ to the βRARE, and consequent induction of endogenous RARβ expression, is an important component in the retinoid anticancer signal. RXRα may also participate in the retinoid signal, but through mechanisms that do not involve RARβ. © 2003 Wiley‐Liss, Inc.
Transforming growth factor β‐1 and amphiregulin act in synergy to increase the production of urokinase‐type plasminogen activator in transformed breast epithelial cells
Authors: Giusti Corinne , Desruisseau Sylvie , Ma Lin , Calvo Fabien , Martin Pierre‐Marie , Berthois Yolande 
Published: May 2003

AbstractAmphireguline (AR) is an epidermal growth factor (EGF)‐related peptide that seems to play an important role in breast cancer progression. We have demonstrated recently that suppression of AR expression in transformed breast epithelial cells considerably reduced both size and neovascularization of tumors developed in nude mice. We show that the reduction of AR expression allowed to an important decrease of the levels of urokinase‐type plasminogen activator (uPA) and transforming growth factor‐beta1 (TGFβ1). According to these data, exogenous AR (10−10 M–10−8 M) stimulated the production of uPA and TGFβ1 in AR antisense‐transfected A2‐15 and A2‐P17F25 cells. The addition of 2 × 10−10 M TGFβ1 into culture medium increased the level of uPA produced by AR‐expressing parental cells but not by A2‐15 and A2‐P17F25 cell clones. Whereas AR alone stimulated uPA production to 200% of control, combined AR and TGFβ1 treatment increased protease level in A2‐15 and A2‐P17F25 cells to 500–600% of control, demonstrating a synergism between TGFβ1 and AR. This was accompanied by an important augmentation of the number of tumoral cells that invaded matrigel in vitro. The synergistic induction of uPA protein resulted of an early and transient augmentation of steady state mRNA level and was blocked in the presence of the MAP kinase kinase inhibitor PD098059, strongly suggesting that synergistic effect of AR and TGFβ1 on uPA expression required MAPK pathway. This data demonstrates concerted action between AR and TGFβ1 that may have profound effect on protease production and consequently on breast cancer progression. © 2003 Wiley‐Liss, Inc.
Physical inactivity, energy intake, obesity and the risk of rectal cancer in Canada
Authors: Mao Yang , Pan Saiyi , Wen Shi Wu , Johnson Kenneth C. ,   The Canadian Cancer Registries Epidemiology Research Group
Published: May 2003

AbstractWe conducted a population‐based case‐control study of 1,447 incident rectal cancer cases and 3,106 population controls aged 20–76 years to assess the effect of recreational physical activity, energy intake and obesity on rectal cancer risk in 7 of 10 Canadian provinces in 1994–97. After adjustment for the effect of various potential confounding factors, total recreational physical activity in the highest quartile was associated with an odds ratio (OR) for rectal cancer risk of 0.88 (95% confidence interval [CI] = 0.64–1.20) in women and 1.15 (95% CI = 0.88–1.49) in men. Women and men in the highest quartile of caloric intake (> = 56,741 and > = 63,143 kJ/week) had ORs of 1.50 (95% CI = 1.00–2.25) and 1.61 (95% CI = 1.13–2.28), respectively. Total dietary fat intake was not associated with a risk of rectal cancer after adjustment for caloric intake. Obesity (BMI > = 30 kg/m2) was associated with an OR of 1.44 (95% CI = 1.06–1.95) for women and 1.78 (95% CI = 1.36–2.34) for men. Men and women with lifetime maximum body mass index (BMI) > = 30 kg/m2 had respective ORs of 1.70 (95% CI = 1.30–2.23) and 1.26 (95% CI = 0.96–1.66). The greatest increase in rectal cancer risk was observed in men and women with simultaneous high energy intake, high BMI and low physical activity. Our study provides evidence that physical inactivity, high energy intake and obesity are associated with the risk of rectal cancer, and there is a probable synergic effect among the 3 risk factors. © 2003 Wiley‐Liss, Inc.
Induction of systemic immunity by expression of interleukin‐23 in murine colon carcinoma cells
Authors: Wang Yan‐Qing , Ugai Shin‐ichi , Shimozato Osamu , Yu Ling , Kawamura Kiyoko , Yamamoto Hiroshi , Yamaguchi Taketo , Saisho Hiromitsu , Tagawa Masatoshi 
Published: May 2003

AbstractInterleukin‐23 (IL‐23), a novel cytokine composed of a newly identified p19 molecule and the p40 subunit of IL‐12, can stimulate the proliferation in vitro of memory T cells. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p19‐linked p40 gene (Colon 26/IL‐23) could produce antitumor effects in inoculated mice. The growth of Colon 26/IL‐23 tumors developed in immunocompetent mice was significantly retarded and the tumors disappeared thereafter. Spleen cells from the mice that received Colon 26/IL‐23 cells produced significant amounts of interferon‐γ, when they were cultured with irradiated Colon 26 but not irrelevant cells. Depletion of CD8+ T cells suppressed the production of interferon‐γ. The mice that had rejected Colon 26/IL‐23 tumors were resistant to subsequent challenge of parent but not irrelevant tumor cells. Colon 26/IL‐23 tumors were not rejected in nude mice but the growth was retarded compared to parent tumors. Treatment of nude mice with anti‐asialo GM1 antibody did not influence the growth of Colon 26/IL‐23 tumors. These data suggest that expression of IL‐23 in tumors produces T cell‐dependent antitumor effects and induces systemic immunity. © 2003 Wiley‐Liss, Inc.
Expression of ADAM‐9 mRNA and protein in human breast cancer
Authors: O'Shea Caroline , McKie Norman , Buggy Yvonne , Duggan Catherine , Hill Arnold D.K , McDermott Enda , O'Higgins Niall , Duffy Michael J. 
Published: May 2003

AbstractThe ADAMs (a disintegrin and metalloprotease) are membrane proteins containing both protease and adhesion domains and thus may be potentially important in cancer invasion and metastasis. The aim of our study was to investigate the distribution and potential clinical significance of ADAM‐9 in breast cancer. ADAM‐9 expression was measured using both reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blotting. ADAM‐9 mRNA was expressed more frequently in both breast carcinomas (72/110, 66%) and fibroadenomas (21/38, 55%) compared to normal breast tissue (6/25, 24%) (p = 0.0004, p = 0.028, respectively). Multiple forms of ADAM‐9 protein were detected by Western blotting, i.e., at 124, 84 and 48 kDa under reducing conditions and at 115, 76, 55, 52 and 46 kDa under nonreducing conditions. The 84 and 55 kDa forms were detected more frequently in the primary cancers compared to normal breast tissue (p < 0.0001, p = 0.0002, respectively). In addition, relative levels of the 84 kDa mature form were significantly higher in the primary cancers than in the fibroadenomas (p = 0.003), while the reverse was found for the 124 kDa precursor form (p = 0.026). In the carcinomas, the 84 kDa form of ADAM‐9 protein was expressed at higher levels in node‐positive than node‐negative cancers (p = 0.05) and correlated positively with HER‐2/neu protein levels (r = 0.313, p = 0.016). This is the first report to describe expression of any ADAM in a large number of human carcinomas. © 2003 Wiley‐Liss, Inc.
Evaluation of hypermethylated tumor suppressor genes as tumor markers in mouth and throat rinsing fluid, nasopharyngeal swab and peripheral blood of nasopharygeal carcinoma patient
Authors: Chang Hsiao Wen , Chan Amy , Kwong Dora Lai Wan , Wei William Ignace , Sham Jonathan Shun Tong , Yuen Anthony Po Wing 
Published: May 2003

AbstractThe purpose of our study was to evaluate the frequency of hypermethylated tumor suppressor genes (TSGs) in peripheral blood, mouth and throat (M&T) rinsing fluid and nasopharyngeal (NP) swabs of nasopharyngeal carcinoma (NPC) patients. Six normal NP tissues, 43 M&T rinsing fluid, 37 NP swabs and 43 peripheral blood from healthy non‐smokers and non‐drinkers without a family history of NPC, and 30 NPC tumors and their matched body fluid were analyzed for the presence of hypermethylated p15, p16, Ras association domain family 1 (RASSF1A), E‐cadherin, and death‐associated protein kinase (DAPK) by methylation‐specific PCR. Sequencing analysis was carried out on selected NPC tumors and body fluid samples. Twenty‐nine (97%) tumors displayed methylation in at least 1 of the 5 genes. The methylation frequencies were 80% for p15, 77% for DAPK, 67% for RASSF1A, 53% for E‐cadherin and 33% for p16. The frequency range of aberrant methylated genes in the body fluids were NP swabs (17–63%) and M&T rinsing fluid (17–50%). Methylation was found in <20% of peripheral blood for each respective gene. Methylation was, however, detected in 1 M&T rinsing fluid in which the primary tumor showed methylation free for RASSF1A. Five healthy individuals exhibited methylation for DAPK, or RASSF1A, or p15 in their body fluid samples. All body fluid samples of healthy controls showed methylation free for E‐cadherin and p16. Epigenetic change is found frequently in NPC and the high detection rate in body fluids suggest its potential application in non‐invasive screening of NPC or detection of residual carcinoma after treatment. © 2003 Wiley‐Liss, Inc.
Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: A phase II study
Authors: Becerra Carlos R. , Frenkel Eugene P. , Ashfaq Raheela , Gaynor Richard B. 
Published: May 2003

AbstractPreclinical and clinical models have demonstrated that cyclooxygenase‐2 (COX‐2) is overexpressed in primary and metastatic colorectal tumors. In preclinical models, there appears to be additive or synergistic effects when combining 5‐Fluorouracil (5‐FU) with nonsteroidal anti‐inflammatory agents (NSAIDs) for the treatment of colorectal neoplasms. This data raised the question as to whether adding a COX‐2 inhibitor to 5‐FU‐based regimens would increase the response rates with an acceptable toxicity profile in patients with metastatic colon cancer. In the current study, patients with metastatic colorectal cancer, who were either untreated or previously treated (more than 1 year ago) with adjuvant 5‐FU and Leucovorin (LV) received 5‐FU and LV (Mayo regimen) in addition to Rofecoxib. Tumor samples from all patients exhibited evidence of moderate COX‐2 over‐expression. 4 patients entered on the study developed upper gastrointestinal bleeding (grade III). Other toxicities included grade II stomatitis (3 patients), grade II thrombocytopenia (1 patient), grade II diarrhea (2 patients) and grade I nausea (1 patient). There were no partial or complete responses in the first 10 patients entered on the study so the study was terminated (probability of success < 0.3 with type 1 error of 0.05 and power of 0.8). Thus, Rofecoxib did not appear to increase antitumor activity and resulted in increased gastrointestinal toxicity when combined with 5‐FU/LV. Future studies will need to consider the added gastrointestinal toxicity of Rofecoxib when combined with chemotherapy for the treatment of patients with colorectal cancer. © 2003 Wiley‐Liss, Inc.
Physical activity and epithelial ovarian cancer risk: A case‐control study in China
Authors: Zhang Min , Lee Andy H. , Binns Colin W. 
Published: May 2003

AbstractA case‐control study was conducted in China during 1999–2000 to investigate the effects of intensity and duration of physical activity on the risk of epithelial ovarian cancer. Cases were 254 patients with histologically confirmed epithelial ovarian cancer. The 652 controls comprised 340 hospital visitors, 261 non‐neoplasm hospital outpatients and 51 women recruited from the community. Physical activity was measured by a validated questionnaire. The risks of ovarian cancer were assessed using multivariate logistic regression analysis accounting for age, demographic, lifestyle and familial factors, hormonal status, family ovarian cancer history and total energy intake. The study found that increasing total physical activity was associated with a lower ovarian cancer risk among Chinese women. The odds ratio was 0.54 (95% CI 0.34–0.87) for high vs. low levels of total weekly metabolic equivalent tasks. Ovarian cancer risk tended to decline with increasing duration of strenuous sports and frequency of activity‐induced sweating among pre‐menopausal women, with adjusted OR 0.13 (95% CI 0.03–0.64) and 0.45 (95% CI 0.24–0.85), respectively. Increasing duration of moderate activity in post‐menopausal women also appeared to be protective against ovarian cancer, with adjusted OR 0.36 (95% CI 0.18–0.73). © 2003 Wiley‐Liss, Inc.
Breast cancer and specific types of oral contraceptives: A large Norwegian cohort study
Authors: Dumeaux Vanessa , Alsaker Elin , Lund Eiliv 
Published: May 2003

AbstractThe aim of our study was to examine the risk of breast cancer according to specific types of estrogens and progestagens in oral contraceptives (OCs) based on the prospective Norwegian Women and Cancer study (NOWAC). Between 1991–97 women aged 30–70 years were drawn at random from the central person register and mailed an invitation and a questionnaire. Women (102,443) were enrolled with follow‐up information collected throughout 1999 by linkage with national registries of cancer, mortality and emigration based on the unique national identification number. Among the 96,362 women included in the present analysis 851 invasive breast cancer were diagnosed. The adjusted risk of breast cancer increased with 25% for ever use of OCs and the risk increased with increasing duration of use (test for trend: p = 0.007). No association between time since last use and breast cancer risk was found after stratification on duration of use. Positive trend was still found for total duration of use among women who used OCs more than 5 years ago. Second generation of OCs had an increased risk with increasing duration of use. Classifying progestagens according to chemical groups, the relative risk increased significantly with increasing cumulative dose of levonorgestrel progestagen. It was difficult to conclude for the other groups due to lack of power. In a multivariate analysis the cumulative dose for all progestagen groups were non‐significant, although we observed a significant increased risk with increasing milligram‐months of estrogen exposure (p = 0.002). In conclusion, the increased risk of breast cancer related with OC formulations could be due mostly to estrogen component. © 2003 Wiley‐Liss, Inc.