bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary exposure and urinary excretion of total N‐nitroso compounds, nitrosamino acids and volatile nitrosamine in inhabitants of high‐ and low‐risk areas for esophageal cancer in southern China
Authors: Lin Kun , Shen Wenying , Shen Zhongying , Wu Yongning , Lu Shihhsin 
Published: October 2002

AbstractWe assessed the exposure of total N‐nitroso compounds (TNOCs) in the inhabitants of high‐ and low‐risk areas for esophageal cancer in southern China. Samples of 24 hr diet and 12 hr overnight urine were collected from 120 male adults in each of the 2 areas, a high‐risk area (Nan'ao County) and a low‐risk area (Lufeng County) for esophageal cancer. Annual standardized mortality rates of esophageal cancer in Nan'ao and Lufeng are 110/106 and 10/106 respectively. The 240 healthy male subjects (35–64 years old) were selected by a 3‐stage random cluster sample procedure. Levels of TNOCs, NAAs and volatile nitrosamines in the samples were measured. The TNOC detection rate (95%) in the diet, the TNOC daily intake (4.25 ± 0.84 μmol), TNOC excretion levels (0.04 ± 0.01 nmol/12 hr) and daily intake of volatile nitrosamines (5.84 ± 0.71 μmol) in the high‐risk area were significantly greater than values in the low‐risk area (A ± B = mean ± SE). The TNOC detection rate in the diet, the TNOC daily intake, TNOC excretion levels and daily intake of volatile nitrosamines in the low‐risk area were 70%, 0.25 ± 0.06 μmol, 0.02 ± 0.01 nmol/12 hr and 3.18 ± 0.31 μmol, respectively. NAA excretion levels showed no difference between the 2 areas (16.3 ± 7.18 μmol/12 hr for Nan'ao and 31.2 ± 26.4 μmol/12 hr for Lufeng). Thus, TNOCs are implicated in the etiology of esophageal cancer in southern China. © 2002 Wiley‐Liss, Inc.
Inhibition of prostate‐specific membrane antigen (PSMA)‐positive tumor growth by vaccination with either full‐length or the C‐terminal end of PSMA
Authors: Kuratsukuri Katsuyuki , Sone Tomomichi , Wang Ching Y. , Nishisaka Nobuyasu , Jones Richard F. , Haas Gabriel P. 
Published: October 2002

AbstractFor experimental immunotherapy of prostate cancer, we used a model system to target a defined region of the extracellular domain of prostate‐specific membrane antigen (PSMA). PSMA is a surface antigen expressed by prostate epithelium that is upregulated approximately 10‐fold in most prostate tumors. We vaccinated BALB/c mice with NIH3T3 cells cotransfected with pST/neo plus pEF‐BOS‐based vectors expressing either the full‐length 750–amino acid human PSMA or only the C‐terminal 180–amino acid region (PSMc). PSMc lies C‐terminal to the transferrin receptor‐like sequence in the extracellular domain of PSMA. BALB/c mice were injected i.p. 4 times at weekly intervals with vaccine cells. Vaccinated mice were then challenged s.c. with Renca/PSMA, a BALB/c renal cell carcinoma line transfected to express human PSMA. Growth of Renca/PSMA tumors was substantially retarded and host survival significantly prolonged in mice prevaccinated with either 3T3/PSMA or 3T3/PSMc. Furthermore, antiserum from vaccinated mice intensely immunocytochemically stained LNCaP, a PSMA‐positive human prostate cancer cell line. In contrast, control mice similarly prevaccinated i.p. with 3T3/neo (NIH3T3 cells transfected with pST/neo alone) developed Renca/PSMA tumors, which were palpable within 2 weeks and lethal by 5 weeks. Serum from 3T3/neo‐vaccinated mice did not immunocytochemically stain LNCaP cells. The antitumor activity induced by vaccination with 3T3/PSMc was also demonstrated via growth inhibition of established LNCaP tumors xenografted in athymic mice following passive transfer of immune serum from vaccinated mice. Our results suggest that vaccination with PSMc induces adaptive humoral activity, which is directed against the extracellular region of human PSMA and can significantly inhibit human prostate cancer growth in athymic mice, and that administration of antibodies to PSMA may provide a passive treatment modality for immunocompromised patients. © 2002 Wiley‐Liss, Inc.
Ectopic expression of herpes simplex virus‐thymidine kinase gene in human non‐small cell lung cancer cells conferred caspase‐activated apoptosis sensitized by ganciclovir
Authors: Chiu Chien‐Chih , Kang Yuan‐Lin , Yang Tsung‐Hsiang , Huang Chih‐Hsin , Fang Kang 
Published: October 2002

AbstractHuman non‐small cell lung cancer (NSCLC) cells were transfected with recombinant prodrug herpes simplex virus type I thymidine kinase (HSV‐tk) cDNA, and the selected clones underwent apoptosis in response to induction by antiviral ganciclovir (GCV). The efficiency of GCV‐induced growth inhibition and the extent of the bystander effect were associated with the expression level of HSV‐TK in stable transfectants. Development in the HSV‐tk/GCV system toward cell death was initiated with cell‐cycle accumulation at S and G2/M phases, immediately followed by the appearance of sub‐G0/G1 cells after drug exposure. To investigate the regulation of cell‐cycle modulators during drug treatment, we analyzed release of the apoptosis initiator cytochrome c and activation of the downstream effectors caspase‐9, caspase‐3 and poly(ADP‐ribose)polymerase 16 hr after GCV sensitization, followed by transient escalation of tumor‐suppressor p53 and cell‐cycle modulators cyclin A and B1 before committing to programmed cell death. Furthermore, tumor regression was proportional to the degree of ectopic expression of the transferred HSV‐tk gene. Our results demonstrate that the HSV‐tk/GCV system effectively inhibits the proliferation of NSCLC cells in vitro and in vivo through potent induction of apoptosis, thus providing a rationale for further development. © 2002 Wiley‐Liss, Inc.
Monocyte chemoattractant protein‐1 expression correlates with macrophage infiltration and tumor vascularity in human esophageal squamous cell carcinomas
Authors: Ohta Masahiro , Kitadai Yasuhiko , Tanaka Shinji , Yoshihara Masaharu , Yasui Wataru , Mukaida Naofumi , Haruma Ken , Chayama Kazuaki 
Published: October 2002

AbstractTumor angiogenesis requires the production of angiogenic factors by tumor and stromal cells. Macrophages are key effectors of angiogenesis and reported to contribute to tumor angiogenesis in several carcinomas. To investigate interactions between tumor cells and macrophages in angiogenesis, we examined macrophage infiltration, tumor vascularity and expression of monocyte chemoattractant protein (MCP)‐1, CC chemokine receptor 2 (CCR2) and vascular endothelial growth factor (VEGF) in 57 archival specimens from patients with esophageal dysplasia (n = 9) and squamous cell carcinomas (n = 48). Expression of MCP‐1 mRNA was also examined by reverse transcriptase‐polymerase chain reaction (RT‐PCR) in 7 esophageal carcinoma cell lines and fresh biopsy specimens from 14 patients. The number of infiltrating macrophages correlated closely with expression of VEGF by tumor cells and with neovascularization. Of the 7 cell lines, 4 (TE‐1, 3, 5 and 13) constitutively expressed MCP‐1 mRNA. In 9 (64.3%) of the 14 patients, MCP‐1 mRNA was expressed at high levels in tumor tissues as compared to normal mucosa. MCP‐1 immunoreactivity increased with the depth of tumor invasion (Tis 0%, T1 26.3%, T2, T3 42.1%). Moreover, macrophage and vessel counts were significantly higher in MCP‐1‐positive tumors than in MCP‐1‐negative tumors. Normal and dysplastic esophageal squamous epithelium showed no staining or faint cytoplasmic staining of MCP‐1. Expression of CCR2 immunoreactivity was detected in the cytoplasm of mononuclear cells but not of vascular endothelial cells. These results suggest that interactions between cancer cells and macrophages are important for tumor angiogenesis. MCP‐1 may play a role in progression of human esophageal carcinoma through its role in angiogenesis. © 2002 Wiley‐Liss, Inc.
CD44 stimulation by fragmented hyaluronic acid induces upregulation of urokinase‐type plasminogen activator and its receptor and subsequently facilitates invasion of human chondrosarcoma cells
Authors: Kobayashi Hiroshi , Suzuki Mika , Kanayama Naohiro , Nishida Takashi , Takigawa Masaharu , Terao Toshihiko 
Published: October 2002

AbstractIt has been established that fragmented hyaluronic acid (HA), but not native high molecular weight HA, can induce angiogenesis, cell proliferation and migration. We have studied the outside‐in signal transduction pathways responsible for fragmented HA‐mediated cancer cell invasion. In our study, we have studied the effects of CD44 stimulation by ligation with HA upon the expression of matrix metalloproteinases (MMPs)‐2 and ‐9 as well as urokinase‐type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI‐1) and the subsequent induction of invasion of human chondrosarcoma cell line HCS‐2/8. Our study indicates that (i) CD44 stimulation by fragmented HA upregulates expression of uPA and uPAR mRNA and protein but does not affect MMPs secretion or PAI‐1 mRNA expression; (ii) the effects of HA fragments are critically HA size dependent: high molecular weight HA is inactive, but lower molecular weight fragmented HA (Mr 3.5 kDa) is active; (iii) cells can bind avidly Mr 3.5 kDa fragmented HA through a CD44 molecule, whereas cells do not effectively bind higher Mr HA; (iv) a fragmented HA induces phosphorylation of MAP kinase proteins (MEK1/2, ERK1/2 and c‐Jun) within 30 min; (v) CD44 is critical for the response (activation of MAP kinase and upregulation of uPA and uPAR expression); and (vi) cell invasion induced by CD44 stimulation with a fragmented HA is inhibited by anti‐CD44 mAb, MAP kinase inhibitors, neutralizing anti‐uPAR pAb, anti‐catalytic anti‐uPA mAb or amiloride. Therefore, our study represents the first report that CD44 stimulation induced by a fragmented HA results in activation of MAP kinase and, subsequently, enhances uPA and uPAR expression and facilitates invasion of human chondrosarcoma cells. © 2002 Wiley‐Liss, Inc.
DCR3 locus is a predictive marker for 5‐fluorouracil‐based adjuvant chemotherapy in colorectal cancer
Authors: Mild Gabriele , Bachmann Felix , Boulay Jean‐Louis , Glatz Katharina , Laffer Urban , Lowy Adam , Metzger Urs , Reuter Jürgen , Terracciano Luigi , Herrmann Richard , Rochlitz Christoph 
Published: October 2002

AbstractAdjuvant chemotherapy reduces the incidence of distant metastasis and increases survival of patients with colorectal cancer. However, predictive markers are needed to define subsets of patients with stage II and III disease that may benefit from adjuvant treatment. A secreted member of the TNF receptor superfamily, the decoy receptor 3 (DcR3), was reported to be amplified in colorectal cancer as a negative regulator of Fas‐mediated apoptosis. We analyzed DcR3 gene copy number and protein expression in a large series of tumors from a randomized multicenter trial of 5‐fluorouracil/mitomycin C (FU/MMC) adjuvant chemotherapy of the Swiss Group for Clinical Cancer Research (SAKK 40/81), using real‐time quantitative PCR and immunohistochemistry on tumor microarrays. Results of gene status and protein expression of DcR3 were correlated with disease‐free and overall survival of patients. We observed amplification of the DcR3 gene in 185/294 (63%) and overexpression of the DcR3 protein in 163/223 (73%) of colorectal tumors. Multivariate analysis showed no prognostic effect of DcR3 gene amplification and protein overexpression. However, adjuvant chemotherapy was significantly more beneficial in patients with normal DcR3 gene copy number than in patients with amplification (DFS: HR 2.84, 95% CI 1.16–6.98, p = 0.02; OS: HR 3.15, 95% CI 1.19–8.32, p = 0.02), whereas DcR3 protein overexpression did not influence the effect of adjuvant chemotherapy (DFS: HR 1.02, 95% CI 0.65–1.60, p = 0.95; OS: HR 0.95, 95% CI 0.61–1.49, p = 0.83). We conclude that amplification of the 20q13 locus is a predictive marker for adjuvant chemotherapy in colorectal cancer. © 2002 Wiley‐Liss, Inc.
Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma
Authors: Diesinger Isabel , Bauer Christine , Brass Nicole , Schaefers Hans‐Joachim , Comtesse Nicole , Sybrecht Gerhard , Meese Eckart 
Published: October 2002

AbstractThere is very limited knowledge about the antibody response against tumor‐expressed antigens in lung cancer. To arrive at a more complete picture of lung cancer antigens, we generated 2 cDNA libraries from squamous cell lung carcinoma and isolated 15 immunogenic antigens using autologous sera. Among the antigens most frequently identified were the lymphoid blast crisis oncogene (LBC), an unknown hypothetical protein and the p53‐binding protein (TP53 BP), which have already been associated with tumor development. Of the immunogenic antigens, 6 map to chromosomes that are frequently altered in squamous cell lung carcinoma. SEREX database analysis showed that 7 of the identified immunogenic antigens have been associated with the humoral immune response in other human tumors. Screening with heterologous sera of patients with lung carcinoma identified 4 antigens, including human protein kinase C and TP53 BP, which have also been found by autologous screening. Only 1 of the 15 identified antigens reacted with any of the 36 control sera, which were taken from individuals without known disease. Sera from adenocarcinoma and large cell carcinoma of the lung were not reactive for the antigens. In summary, using 2 newly established cDNA libraries, we isolated 15 novel antigens, which were subsequently evaluated for the frequency of their corresponding antibodies in autologous, normal and heterologous sera; their chromosomal localization; and their correlation with survival after surgery. © 2002 Wiley‐Liss, Inc.
Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population
Authors: Serra Iván , Yamamoto Masaharu , Calvo Alfonso , Cavada Gabriel , Báez Sergio , Endoh Kazuo , Watanabe Hidenobu , Tajima Kazuo 
Published: October 2002

AbstractWe explored the risk factors for gallbladder cancer and explanations for its sharp and constant incidence increase in Chile since the 1970s. We compared 114 consecutive patients with verified gallbladder cancer, diagnosed 1992–1995, to 114 matched hospital patients with gallstones, using conditional logistic regression analysis. Low education showed a nonsignificant positive relationship with gallbladder cancer [odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.8–6.2], and low socioeconomic level showed a significant relationship (OR = 5.0, 95% CI 1.5–17.3). A very long history of gallstone disease was significantly more prevalent among cases (OR = 11.0, 95% CI 1.4–85.2). Significant red chili pepper consumption was observed in gallbladder cancer patients (OR = 2.9, 95% CI 1.6–5.2). Low intake of both fresh fruit and sugar as soft drinks was associated with gallbladder cancer, with ORs of 6.4 (95% CI 1.4–30.3) and 3.6 (95% CI 1.3–10.1), respectively. Multivariate analysis kept only a very low socioeconomic status and red chili pepper consumption as significant independent risk factors for gallbladder cancer, ORs of 6.3 (95% CI 1.7–23.0) and 3.2 (95% CI 1.7–5.9). Longstanding gallstone cases were removed from the multivariate model because all were in the low and very low socioeconomic groups, reinforcing the association. Patients with gallbladder cancer differed from matched controls by exhibiting lower socioeconomic levels, having a much longer history of gallstone disease and presenting a dietary pattern characterized by high red chili pepper consumption and low fresh fruit intake. © 2002 Wiley‐Liss, Inc.
Oxidative DNA damage by a common metabolite of carcinogenic nitrofluorene andN‐acetylaminofluorene
Authors: Murata Mariko , Yoshiki Yumiko , Tada Mariko , Kawanishi Shosuke 
Published: October 2002

AbstractBoth carcinogenic NF and AAF are metabolized to a commonN‐hydroxy metabolite, N‐OH‐AF. We investigated oxidative DNA damage by N‐OH‐AF, using32P‐labeled human DNA fragments from the humanp53andp16tumor‐suppressor genes and the c‐Ha‐ras‐1 protooncogene. N‐OH‐AF caused Cu(II)‐mediated DNA damage, and endogenous reductant NADH markedly enhanced this process. Catalase and bathocuproine, a Cu(I)‐specific chelator, decreased the DNA damage, suggesting the involvement of H2O2and Cu(I). N‐OH‐AF induced piperidine‐labile lesions frequently at thymine and cytosine residues. With formamidopyrimidine‐DNA glycosylase treatment, N‐OH‐AF induced cleavage at guanine residues, especially of the ACG sequence complementary to codon 273, a well‐known hot spot of thep53gene. N‐OH‐AF dose‐dependently induced 8‐oxodG formation in the presence of Cu(II) and NADH. Treatment with N‐OH‐AF increased amounts of 8‐oxodG in HL‐60 cells compared to the H2O2‐resistant clone HP100, supporting the involvement of H2O2. The present study demonstrates that theN‐hydroxy metabolite of NF and AAF induces oxidative DNA damage through H2O2in both a cell‐free system and cultured human cells. We conclude that oxidative DNA damage may play an important role in the carcinogenic process of NF and AAF in addition to previously reported DNA adduct formation. © 2002 Wiley‐Liss, Inc.
Cytoplasmic and/or nuclear accumulation of the β‐catenin protein is a frequent event in human osteosarcoma
Authors: Haydon Rex C. , Deyrup Andrea , Ishikawa Akira , Heck Robert , Jiang Wei , Zhou Lan , Feng Tao , King David , Cheng Hongwei , Breyer Benjamin , Peabody Terrance , Simon Michael A. , Montag Anthony G. , He Tong‐Chuan 
Published: October 2002

AbstractThe molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of β‐catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of β‐catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for β‐catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the β‐catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of β‐catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating β‐catenin signaling in osteosarcoma. In our survival analysis, β‐catenin deregulation conferred a hazard ratio of 1.05, indicating that β‐catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, β‐catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of β‐catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma. © 2002 Wiley‐Liss, Inc.
Continuing rising trend in oesophageal adenocarcinoma
Authors: Powell Jean , McConkey Chris C. , Gillison E. Walford , Spychal Robert T. 
Published: October 2002

AbstractOur study provides an update of the incidence of oesophageal cancer in the West Midland region of England and Wales from 1992–96. A total of 2,671 cases of oesophageal cancer were identified during the 5‐year study period, with an age‐standardised annual incidence (ASR) of 5.24 per 100,000 (95% CI: 5.02, 5.45). Similar numbers of adenocarcinoma and squamous cell carcinoma were found. Only 152 (5.6%) had no histology. There was a 5‐fold difference in age‐standardised annual incidence rates between males and females for adenocarcinoma of oesophagus, but no gender difference for squamous cell carcinoma. The parallel but higher ASR in males compared to females for adenocarcinoma of both oesophagus and cardia merits further investigation. The similarities in the patterns of age‐ and sex‐specific rates and in the socioeconomic profiles could indicate a common aetiology for adenocarcinoma of oesophagus and gastric cardia. Quality control in Cancer Registries needs to focus on the accuracy and consistency of subsite classification to ensure that trends in incidence are identified. In the absence of accurate subsite classification of stomach cancers, the proportions of adenocarcinoma and squamous cell carcinoma of oesophagus (or the absolute rate of adenocarcinoma of oesophagus) may provide a useful tool in indicating whether adenocarcinoma of gastric cardia is likely to be increasing in incidence. © 2002 Wiley‐Liss, Inc.
Microsatellite instability in thorotrast‐induced human intrahepatic cholangiocarcinoma
Authors: Liu Duo , Momoi Hirohito , Li Li , Ishikawa Yuichi , Fukumoto Manabu 
Published: October 2002

AbstractThorotrast, a colloidal suspension of radioactive 232ThO2 that emits α particles, was used as a radiographic contrast during World War II. It is known to induce liver cancers, most frequently ICC, decades after injection. Since radiation induces genomic instability, we analyzed MSI in Thorotrast‐induced ICC. The frequency of MSI+ cases was 62.5% in Thorotrast ICC, whereas it was 22.7% in non‐Thorotrast ICC. However, frameshift mutations of mononucleotide repeats were not observed in Thorotrast ICC. In addition, the MSI+ phenotype was not associated with the quantity of Thorotrast deposited or the latency period of ICC induction. Promoter regions of both the hMLH1 and the hMSH2 MMR genes tended to be hypermethylated in the tumor part compared to the adjacent nontumor part in Thorotrast ICC. Methylation of the hMLH1 promoter was associated with the MSI+ phenotype in Thorotrast ICC. In contrast, methylation status of these promoter regions was not related to MSI in non‐Thorotrast ICC cases. These findings suggest that MSI induced by exposure to Thorotrast mainly reflects clonal expansion of cancer cells and is partly due to inactivation of hMLH1 by hypermethylation. © 2002 Wiley‐Liss, Inc.
Both the epitope specificity and isotype are important in the antitumor effect of monoclonal antibodies against Her‐2/neu antigen
Authors: Kim Kwang‐Mi , Shin Eun‐Young , Moon Jeoung‐Hyun , Heo Tae‐Hwe , Lee Joon Youb , Chung Yeonseok , Lee Yoon‐Jung , Cho Hyun‐Mi , Shin Seung‐Uon , Kang Chang‐Yuil 
Published: October 2002

AbstractThe Her‐2/neu oncogene, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. Antibodies directed to this molecule have been previously shown to have an antitumor effect in vivo. In an attempt to understand the mechanisms of the antitumor activity, we generated 2 monoclonal antibodies (mAbs), HRO G1 and HRT G1, that recognize different epitopes on Her‐2/neu. Both of the mAbs bound HER2/neu on the tumor surface, resulting in phosphorylation of HER2/neu. We also generated IgG2a and IgG2b mAbs from these 2 mAbs, respectively. The results of in vitro studies showed that these anti‐Her‐2/neu mAbs could not inhibit the growth of the tumor cells that express Her‐2/neu molecules by themselves. However, in an antibody‐dependent cellular cytotoxicity study using mouse splenocytes as effector cells, HRT mAbs had antitumor activities superior to those of HRO mAbs, indicating that the epitope specificity may also partake in antibody‐dependent cellular cytotoxicity with antibody isotype. In a complement‐dependent cytotoxicity study, the IgG2a and IgG2b mAbs showed stronger effects than IgG1 isotype mAbs irrespective of the epitope specificities. The results of in vivo studies also showed that HRT mAbs had superior antitumor activity to those of HRO mAbs. The antitumor activity was most prominent in the HRT G2b isotype among HRT mAbs. HRT G1 also showed a moderate antitumor effect, while HRT G2a showed only slight inhibition effect. These data indicate that both the epitope specificity and the differences in Fc region of mAbs could play important roles in the antitumor activities. © 2002 Wiley‐Liss, Inc.