bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful cancer vaccine therapy for carcinoembryonic antigen (CEA)‐expressing colon cancer using genetically modified dendritic cells that express CEA and T helper‐type 1 cytokines in CEA transgenic mice
Authors: Ojima Toshiyasu , Iwahashi Makoto , Nakamura Masaki , Matsuda Kenji , Nakamori Mikihito , Ueda Kentaro , Naka Teiji , Ishida Koichiro , Primus F. James , Yamaue Hiroki 
Published: November 2006

AbstractThis study was designed to determine whether the vaccination of genetically modified dendritic cells (DCs) simultaneously expressing carcinoembryonic antigen (CEA), granulocyte macrophage colony‐stimulating factor (GM‐CSF) and interleukin 12 (IL‐12) can overcome the peripheral T‐cell tolerance to CEA and thereby elicit a therapeutic response in CEA transgenic mice. CEA transgenic mice were immunized once by subcutaneous injection with DCs adenovirally transduced with CEA and T helper‐type 1 cytokine genes. The cytotoxic activity of spleen cells against CEA‐expressing tumors, MC38‐CEA, in the mice immunized with DCs expressing CEA (DC‐AxCACEA) was higher than that in those immunized with DCs‐AxCALacZ (p < 0.0001), and was augmented by the cotransduction with the GM‐CSF/IL‐12 gene (p < 0.05). The vaccination with DC‐AxCACEA/GM‐CSF/IL‐12 could elicit a more potent therapeutic immunity than the vaccination with DC‐AxCACEA in subcutaneous tumor models (p < 0.0001), and 4 of 5 mice showed a complete eradication of the subcutaneous tumors in these vaccination groups. Even in a large tumor model, this vaccination therapy completely eliminated the subcutaneous tumors in all mice. This antitumor activity mostly vanished with the depletion of CD8+ T cells and NK cells in vivo and was completely abrogated with the depletion of CD4+ T cells. A histopathological examination showed no evidence of an autoimmune reaction. No other adverse effects were observed. This vaccination strategy resulted in the generation of highly efficient therapeutic immune responses against MC38‐CEA in the absence of autoimmune responses and demonstrated no adverse effects, and may therefore be useful for future clinical applications as a cancer vaccine therapy. © 2006 Wiley‐Liss, Inc.
Alcohol intake and colorectal cancer risk: A dose–response meta‐analysis of published cohort studies
Authors: Moskal Aurélie , Norat Teresa , Ferrari Pietro , Riboli Elio 
Published: November 2006

AbstractThe epidemiologic evidence support that alcohol intake might be associated with increased colorectal cancer risk. However, the results by anatomic site in the large bowel are inconsistent. We conducted a meta‐analysis of prospective cohort studies published between 1990 and June 2005 on the relationship between alcohol intake and colon and rectal cancer. We quantified associations with colon and rectal cancer using meta‐analysis of relative risk (RR) associated to the highest versus the lowest category of alcohol intake and meta‐analysis of study‐specific dose–response slopes using fixed or random effect models depending on the heterogeneity of effects among studies. Sixteen prospective cohort studies including more than 6,300 patients with colorectal cancer were eligible for inclusion. High alcohol intake was significantly associated with increased risk of colon (RR = 1.50; 95% CI = 1.25, 1.79) and rectal cancer (RR = 1.63; 95% CI = 1.35, 1.97) when comparing the highest with the lowest category of alcohol intake, equivalent to a 15% increase of risk of colon or rectal cancer for an increase of 100 g of alcohol intake per week. The relationship did not differ significantly by anatomical site (colon, rectum). Using meta‐regression analysis, we identified geographical area where the study was conducted as a possible source of between‐study heterogeneity of effects among studies. Lifestyle recommendations for prevention of colorectal cancer should consider limiting alcohol intake. © 2006 Wiley‐Liss, Inc.
Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival
Authors: Zell Jason A. , Ignatenko Natalia A. , Yerushalmi Hagit F. , Ziogas Argyrios , Besselsen David G. , Gerner Eugene W. , Anton‐Culver Hoda 
Published: November 2006

AbstractElevated polyamine and nitric oxide levels (both derived from arginine) promote tumorigenesis, whereas non‐steroidal anti‐inflammatory drugs (NSAIDs) inhibit colorectal cancer (CRC) incidence in experimental and epidemiologic studies. We investigated dietary arginine‐induced intestinal tumorigenesis and NSAID‐inhibitory effects in ApcMin/+ mice differentially expressing nitric oxide synthase‐2 (Nos2). We also studied effects of estimated arginine exposures through meat consumption on tumor characteristics and survival in human CRC cases. Dietary arginine increased high‐grade colon adenoma incidence in ApcMin/+Nos2+/+ mice, but not in Nos2 knockout mice. Additionally, celecoxib suppressed intestinal steady state ornithine decarboxylase RNA levels (p < 0.001), induced steady state spermidine/spermine N1‐acetyltransferase RNA levels (p = 0.002), decreased putrescine levels (p = 0.04) and decreased tumor number in the small intestines of ApcMin/+Nos2+/+ mice (p = 0.0003). Five hundred and eleven cases from our NCI‐supported CRC gene‐environment study were analyzed based on self‐reported meat (as a surrogate for arginine) consumption. Familial CRC cases (n = 144) in the highest meat consumption quartile (Q4) had no statistically significant differences in tumor grade compared to cases in Q1–Q3 (p = 0.32); however, they were observed to have decreased overall survival (OS) (10‐year OS = 42% vs. 65%; p = 0.017), and increased risk of death in an adjusted analysis (hazards ratio [HR] = 2.24; p = 0.007). No differences in tumor grade, OS or adjusted HR were observed for sporadic CRC cases (n = 367) based on meat consumption. Our results suggest important roles for arginine and meat consumption in CRC pathogenesis, and have implications for CRC prevention. © 2006 Wiley‐Liss, Inc.
The prognostic significance of thymidylate synthase and dihydropyrimidine dehydrogenase in colorectal cancer of 303 patients adjuvantly treated with 5‐fluorouracil
Authors: Jensen Søren Astrup , Vainer Ben , Sørensen Jens Benn 
Published: November 2006

AbstractCytotoxic effect of 5‐fluorouracil 5‐FU is mediated through inhibition of thymidylate synthase (TS), and 5‐FU is catabolised by dihydropyrimidine dehydrogenase (DPD). Efficacy of 5‐FU may therefore depend on the TS and DPD activity of colorectal cancer. Archival tumour specimens from 303 consecutive patients were analysed for the expression of TS and DPD using immunohistochemistry. All patients were completely resected for colorectal cancer stages II–III and have subsequently received adjuvant treatment with 5‐FU. In a multivariate analysis adjusting for the impact of bowel obstruction and vascular tumour invasion, diffuse TS pattern was significantly associated with increased risk of recurrence (hazard ratio (HR) = 1.9; 95% confidence interval (CI): 1.1–3.2; p = 0.02), but without significant association to death (HR = 1.6; 95% CI: 0.9–2.8; p = 0.08). High TS intensity was not significantly associated with lower risk of recurrence (HR = 0.6; 95% CI: 0.3–1.1; p = 0.07) or death (HR = 0.6; 95% CI: 0.3–1.2; p = 0.2). High DPD intensity was significantly associated with increased risk of recurrence (HR = 1.5; 95% CI: 1.1–2.3; p = 0.03) and death (HR = 1.6; 95% CI: 1.1–2.5; p = 0.02). Patients with a combination of low TS and high DPD intensity were at significantly increased risk of both recurrence (HR = 2.1; 95% CI: 1.0–4.2; p = 0.04) and death (HR = 2.0; 95% CI: 1.0–4.0; p = 0.05). No relationship between tolerability and toxicity of 5‐FU and TS and DPD expression was found. It is concluded that characterizing colorectal carcinomas by TS and DPD expression may disclose subsets of patients with significantly greater risk of disease recurrence and early death. This may be utilized in the selection of patients for treatment approaches and for decision on follow‐up programs. © 2006 Wiley‐Liss, Inc.
Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivationviaarginine deiminase
Authors: Yoon Cheol‐Yong , Shim Young‐Jun , Kim Eun‐Ho , Lee Ju‐Han , Won Nam‐Hee , Kim Jeong‐Hun , Park In‐Sun , Yoon Duck‐Ki , Min Bon‐Hong 
Published: November 2006

AbstractRecently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ASS, which enables tumor cells to recycle citrulline to arginine. Thus, we examined the expression levels of ASS in various cancer cells and found that it is low in renal cell carcinoma (RCC) cells, rendering the cells highly sensitive to arginine deprivation by ADI treatment. Immunohistochemical analysis revealed that in biopsy specimens from RCC patients (n= 98), the expression of ASS is highly demonstrated in the epithelium of normal proximal tubule but not seen in tumor cells. Furthermore, RCC cells treated with ADI showed remarkable growth retardation in a dose dependent manner. ADI also exertedin vivoantiproliferative effect on the allografted renal cell carcinoma (RENCA) tumor cells and prolonged the survival of tumor‐bearing mice. Histological examination of the tumors revealed that tumor angiogenesis and vascular endothelial growth factor (VEGF) expression were significantly diminished by ADI administration. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of RCC in ways of inhibitions of arginine availability and neovascularization. © 2006 Wiley‐Liss, Inc.
High resolution tiling‐path BAC array deletion mapping suggests commonly involved 3p21‐p22 tumor suppressor genes in neuroblastoma and more frequent tumors
Authors: Hoebeeck Jasmien , Michels Evi , Menten Björn , Van Roy Nadine , Eggert Angelika , Schramm Alexander , De Preter Katleen , Yigit Nurten , De Smet Els , De Paepe Anne , Laureys Geneviève , Vandesompele Jo , Speleman Frank 
Published: November 2006

AbstractThe recurrent loss of 3p segments in neuroblastoma suggests the implication of 1 or more tumor suppressor genes but thus far few efforts have been made to pinpoint their detailed chromosomal position. To achieve this goal, array‐based comparative genomic hybridization was performed on a panel of 23 neuroblastoma cell lines and 75 primary tumors using a tiling‐path bacterial artificial chromosome array for chromosome 3p. A total of 45 chromosome 3 losses were detected, including whole chromosome losses, large terminal deletions and interstitial deletions. The latter, observed in cell lines as well as a number of distal deletions detected in primary tumors, allowed us to demarcate 3 minimal regions of loss of 3.6 Mb [3p21.31‐p21.2, shortest regions of overlap (SRO)1], 1.4 Mb (3p22.3‐3p22.2, SRO2) and 3.8 Mb (3p25.3‐p25.1, SRO3) in size. The present data significantly extend previous findings and now firmly establish critical regions on 3p implicated in neuroblastoma. Interestingly, the 2 proximal regions coincide with previously defined SROs on 3p21.3 in more frequent tumors including lung and breast cancer. As such, similar tumor suppressor genes may play a critical role in development or progression of a variety of neoplasms, including neuroblastoma. © 2006 Wiley‐Liss, Inc.
RhoB is frequently downregulated in non‐small‐cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line
Authors: Sato Naohito , Fukui Takayuki , Taniguchi Tetsuo , Yokoyama Toshihiko , Kondo Masashi , Nagasaka Tetsuro , Goto Yasuhiro , Gao Wentao , Ueda Yuichi , Yokoi Kohei , Minna John D. , Osada Hirotaka , Kondo Yutaka , Sekido Yoshitaka 
Published: November 2006

AbstractIdentification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non‐small‐cell lung cancer (NSCLC) cell line, NCI‐H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed RhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly‐ or moderately‐differentiated adenocarcinomas than in well‐differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoB indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC. © 2006 Wiley‐Liss, Inc.
Selective cyclooxygenase‐2 inhibitor downregulates the paracrine epithelial–mesenchymal interactions of growth in scirrhous gastric carcinoma
Authors: Yashiro Masakazu , Nakazawa Kazunori , Tendo Masashige , Kosaka Kinshi , Shinto Osamu , Hirakawa Kosei 
Published: November 2006

AbstractThe importance of cancer‐mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase‐2 (COX‐2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX‐2 inhibitors, effect of COX‐2 inhibitor on the paracrine epithelial–mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM‐2M, gastric fibroblasts, NF‐21, and COX‐2 inhibitor, JTE‐522, were used. Growth‐interaction was examined by calculating the number of cancer cells or by measuring [3H] thymidine incorporation of cancer cells. Effect of JTE‐522 on KGF expression from NF‐21 cells and OCUM‐2M cells was analyzed by ELISA and RT‐PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE‐522 at the concentrations of 10−5 and 10−6 M significantly decreased the growth‐stimulating activity of gastric fibroblasts. JTE‐522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE‐522 significantly decreased the size of xenografted tumor coinoculated with OCUM‐2M cells and NF‐21 cells in nude mice. JTE‐522 decreased COX‐2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX‐2 inhibitor, JTE‐522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial–mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts. © 2006 Wiley‐Liss, Inc.
MDM2 SNP309 T>G alone or in combination with the TP53 R72P polymorphism does not appear to influence disease expression and age of diagnosis of colorectal cancer in HNPCC patients
Authors: Talseth Bente A. , Meldrum Cliff , Suchy Janina , Kurzawski Grzegroz , Lubinski Jan , Scott Rodney J. 
Published: November 2006

AbstractDisease expression in hereditary nonpolyposis colorectal cancer (HNPCC) cannot be readily explained by mutation site in the respective DNA mismatch repair genes associated with this disorder. One explanation is the role of modifying genes that can either promote or prevent disease development on a background of increased risk. Two single nucleotide polymorphisms in MDM2 and TP53 have been shown to be associated with younger ages of disease onset in HNPCC (TP53) and Li‐Fraumeni syndrome (MDM2). In this study 220 HNPCC patients were examined, from Australia and Poland, all characterized at the molecular level to determine the frequency of the MDM2 SNP309 T>G and to assess its influence on disease expression. The results were then pooled with the results of a previous study to assess the combined influence of the MDM2 SNP309 T>G and TP53 SNP R72P. A significant difference was observed between CRC patients and unaffected MMR gene mutation carriers over the age of 45 years (p = 0.01). The unaffected MMR gene mutation carriers over the age of 45 years who carry the G allele have a reduced risk of developing CRC. The results indicate that the MDM2 SNP309, alone or in combination with TP53 R72P, does not influence age of diagnosis of CRC in individuals with HNPCC. In conclusion, the data indicates the G allele of MDM2 SNP309 might have a protective effect on disease development in HNPCC patients and that age of diagnosis of CRC is not associated with MDM2 SNP309 or TP53 R72P either as single SNPs or combined. © 2006 Wiley‐Liss, Inc.
Comprehensive evaluation of genetic variation in the IGF1 gene and risk of prostate cancer
Authors: Johansson Mattias , McKay James D. , Stattin Pär , Canzian Federico , Boillot Catherine , Wiklund Fredrik , Adami Hans‐Olov , Bälter Katarina , Grönberg Henrik , Kaaks Rudolf 
Published: November 2006

AbstractInsulin‐like growth factor‐I (IGF1) stimulates cell proliferation, decreases apoptosis, and has been implicated in cancer development. Epidemiological studies have shown elevated levels of circulating IGF1 to be associated with increased risk of prostate cancer. To what extent genetic variation in the IGF1 gene is related to prostate cancer risk is largely unknown. We performed a comprehensive haplotype tagging (HT) assessment of single nucleotide polymorphisms (SNPs) representing the common haplotype variation in the IGF1 gene. We genotyped 10 SNPs (9 haplotype tagging SNPs (htSNPs)) within Cancer Prostate in Sweden (CAPS), a case–control study of 2,863 cases and 1,737 controls, in order to investigate if genetic variation in the IGF1 gene is associated with prostate cancer risk. Three haplotype blocks were identified across the IGF1 gene and 9 SNPs were selected as haplotype tagging SNPs. Common haplotypes in the block covering the 3′ region of the IGF1 gene showed significant global association with prostate cancer risk (p = 0.004), with one particular haplotype giving an odds ratio of 1.46 (95% CI = 1.15–1.84, p = 0.002). This haplotype had a prevalence of 5% in the study population. Our results indicate that common variation in the IGF1 gene, particularly in the 3′ region, may affect prostate cancer risk. Further studies on genetic variations in the IGF1 gene in relation to prostate cancer risk as well as to circulating levels of IGF1 are needed to confirm this novel finding. © 2006 Wiley‐Liss, Inc.
Selective cytotoxicity of benzyl isothiocyanate in the proliferating fibroblastoid cells
Authors: Miyoshi Noriyuki , Uchida Koji , Osawa Toshihiko , Nakamura Yoshimasa 
Published: November 2006

AbstractIn the present study, experiments using presynchronization culture cells demonstrated that benzyl ITC (BITC), previously isolated from a tropical papaya fruit extract, induced the cytotoxic effect preferentially in the proliferating human colon CCD‐18Co cells to the quiescent ones. Quiescent CCD‐18Co cells were virtually unaffected by BITC and marginal cytotoxicity was observed at 15 μM. We observed that BITC dramatically induced the p53 phosphorylation and stabilization only in the quiescent (G0/G1 phase‐arrested) cells, but not significantly in the proliferating human colon CCD‐18Co cells when compared with quiescent ones. We also observed ataxia telangiectasia‐mutated (ATM) phosphorylation in the quiescent cells. The BITC‐induced p53 phosphorylation was counteracted by caffeine treatment, implying the involvement of an ATM/ataxia telangiectasia and Rad3‐related kinase signaling pathway. Moreover, downregulation of p53 by a siRNA resulted in the enhancement of susceptibility to undergo apoptosis by BITC. We also showed here that depletion of p53 abrogated G0/G1 arrest accompanied by the declined expression of p21waf1/cip1 and p27kip1 in CCD‐18Co cells. In conclusion, we identified p53 as a potential negative regulator of the apoptosis induction by BITC in the normal colon CCD‐18Co cells through the inhibition of cell‐cycle progression at the G0/G1 phase. © 2006 Wiley‐Liss, Inc.
Association of interleukin‐1 gene polymorphisms with gastric cancer: A meta‐analysis
Authors: Wang Ping , Xia Harry Hua‐Xiang , Zhang Jian‐Ying , Dai Li‐Ping , Xu Xue‐Qin , Wang Kai‐Juan 
Published: November 2006

AbstractPrevious studies on the association between interleukin‐1 (IL‐1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL‐1 genotype and gastric caner by systematically reviewing the risk of the original studies. Thirty‐nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta‐analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL‐1B–511T, −31C, +3954T and IL‐1RN*2 was 1.26 (95% confidence interval (CI): 1.03–1.55), 1.00 (95% CI: 0.82–1.22), 1.37 (95% CI: 0.94–2.00) and 1.20 (95% CI: 1.01–1.41), respectively. A stratified analysis showed that IL‐1B–511T was associated with an increased risk of gastric cancer (intestinal type) (OR = 1.76, 95% CI: 1.12–2.57). Moreover, IL‐1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR = 1.30, 95% CI: 1.09–1.54). In conclusion, IL‐1B–511 and IL‐1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer. © 2006 Wiley‐Liss, Inc.
Genomic analysis of the 8p11‐12 amplicon in familial breast cancer
Authors: Melchor Lorenzo , Garcia Maria J. , Honrado Emiliano , Pole Jessica C.M. , Alvarez Sara , Edwards Paul A.W. , Caldas Carlos , Brenton James D. , Benítez Javier 
Published: November 2006

AbstractAmplification of 8p11‐12 has been recurrently reported in sporadic breast cancer. These studies define a complex molecular structure with a set of minimal amplified regions, and different putative oncogenes that show a strong correlation between amplification and over‐expression such as ZNF703/FLJ14299, SPFH2/C8orf2, BRF2 and RAB11FIP. However, none of these studies were carried out on familial breast malignancies. We have studied the incidence, molecular features and clinical value of this amplification in familial breast tumors associated with BRCA1, BRCA2 and non‐BRCA1/2 gene mutations. We detected 9 out of 80 familial tumors with this amplicon by chromosomal comparative genomic hybridization. Next, we used a high‐resolution comparative genomic hybridization array covering the 8p11‐12 region to characterize this chromosomal region. This approach allowed us to define 2 cores of common amplification that largely overlap with those reported in sporadic tumors. Our findings confirm the molecular complexity of this chromosomal region and indicate that this genomic event is a common alteration in breast cancer, present not only in sporadic but also in familial tumors. Finally, we found correlation between the 8p11‐12 amplification and proliferation (Ki‐67) and cyclin E expression, which further proves in familial tumors the poor prognosis association previously reported in sporadic breast cancer. © 2006 Wiley‐Liss, Inc.