bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors
Authors: Möllemann Maria , Wolter Marietta , Felsberg Jörg , Collins V. Peter , Reifenberger Guido 
Published: September 2004

AbstractAllelic losses on the chromosome arms 1p and 19q have been associated with favorable response to chemotherapy and good prognosis in anaplastic oligodendroglioma patients, but the molecular mechanisms responsible for this relationship are as yet unknown. The DNA repair enzyme O6‐methylguanine DNA methyltransferase (MGMT) may cause resistance to DNA‐alkylating drugs commonly used in the treatment of anaplastic oligodendrogliomas and other malignant gliomas. We report on the analysis of 52 oligodendroglial tumors for MGMT promoter methylation, as well as mRNA and protein expression. Using sequencing of sodium bisulfite‐modified DNA, we determined the methylation status of 25 CpG sites within the MGMT promoter. In 46 of 52 tumors (88%), we detected MGMT promoter hypermethylation as defined by methylation of more than 50% of the sequenced CpG sites. Real‐time reverse transcription‐PCR showed reduced MGMT mRNA levels relative to non‐neoplastic brain tissue in the majority of tumors with hypermethylation. Similarly, immunohistochemical analysis showed either no or only small fractions of MGMT positive tumor cells. MGMT promoter hypermethylation was significantly more frequent and the percentage of methylated CpG sites in the investigated MGMT promoter fragment was significantly higher in tumors with loss of heterozygosity on chromosome arms 1p and 19q as compared to tumors without allelic losses on these chromosomes arms. Taken together, our data suggest that MGMT hypermethylation and low or absent expression are frequent in oligodendroglial tumors and likely contribute to the chemosensitivity of these tumors.
Fruits, vegetables and risk of renal cell carcinoma: A prospective study of Swedish women
Authors: Rashidkhani Bahram , Lindblad Per , Wolk Alicja 
Published: September 2004

AbstractFindings of epidemiologic studies on the relationship between fruit and vegetable consumption and renal cell carcinoma (RCC) risk have been inconclusive. To study the association between fruits and vegetables and risk of RCC in a population‐based prospective cohort study of Swedish women, we collected dietary information from 61,000 women age 40–76 years by a food‐frequency questionnaire. During 13.4 years of follow‐up 122 women developed RCC. Cox proportional hazards models were used to estimate relative risks (RR) with 95% confidence interval (CI). Women consuming 5 or more servings of fruit and vegetables daily had a relative risk of 0.59 (95% CI = 0.26–1.34) in comparison to them consuming less than once daily. When fruits and vegetables were examined separately, those who consumed more than 75 servings per month of fruits or vegetables had multivariate relative risk of 0.59 (95% CI = 0.27–1.25) and 0.60 (95% CI = 0.31–1.17) respectively, compared to those consuming 11 or less servings per month. Within the group of fruits, the strongest inverse association was observed for banana (p = 0.07 by Wald test). The risk of RCC increased monotonically with increasing intake frequencies of fruit juice (p‐value for trend = 0.10). Within the group of vegetables, the strongest inverse association was observed for root vegetables (p = 0.03 by Wald test). The risk of RCC decreased with increasing consumption frequencies of white cabbage (p for trend = 0.07). Frequent consumption of salad vegetables (once or more per day) decreased the risk by 40% (RR = 0.60; 95% CI = 0.30–1.22), in comparison to no consumption. Our results suggested that high consumption of fruits and vegetables might be associated with reduced risk of RCC.
Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors
Authors: Spangler E. , Zeigler‐Johnson C.M. , Malkowicz S.B. , Wein A.J. , Rebbeck T.R. 
Published: September 2004

AbstractGenetic factors may be used not only to assess risk of prostate cancer development but also to evaluate prostate cancer outcomes including clinical prognosis, treatment methods, and treatment response. To assess the role of family history on prostate cancer outcomes, we evaluated tumor characteristics, diagnostic precursors and biochemical (prostate specific antigen) relapse‐free survival in men with and without a family history of prostate cancer. A total of 684 prostate cancer cases unselected for family history were identified from an ongoing hospital based prostate cancer case‐control study between 1995 and 2002. Self‐reported family history was grouped within the following categories: none, any, moderate (one affected first or second degree relative) and high (2 or more affected first or second degree relatives). We further considered groups defined by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor stage was not significantly associated with any (odds ratio [OR] = 1.43 95% confidence interval [CI] = 1.00–2.05) or moderate (OR = 1.48, 95% CI = 1.0‐2.19) family histories. Men diagnosed before age 60, however, had higher tumor stages if they had any (OR = 2.19, 95% CI = 1.28–3.75) or moderate (OR = 2.15, 95% CI = 1.2–3.9) family histories. Men diagnosed after age 60 with any family history were significantly more likely to experience biochemical (PSA) failure (Hazard ratio [HR] = 2.60, 95%CI = 1.08–6.25). Men with any and moderate family histories were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI = 1.25–4.95 and HR = 2.46, 95% CI = 1.17–5.16, respectively). Moderate family history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI = 1.06–4.34). Our results suggest that a family history of prostate cancer may be associated with predictors of clinical outcome in prostate cancer cases unselected for a family history of prostate cancer.
JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats
Authors: Wei Min , Morimura Keiichirou , Wanibuchi Hideki , Shen Jun , Salim Elsayed I. , Moku Masaharu , Hakoi Katsuo , Fukushima Shoji 
Published: September 2004

AbstractWe have previously demonstrated that JTE‐522, a selective cyclooxygenase‐2 (COX‐2) inhibitor, inhibited development of aberrant crypt foci (ACF) in rats, a putative preneoplastic lesion in colon, and suggested its inhibitory potential in rat colon carcinogenesis. To evaluate the chemopreventive properties of JTE‐522, the present study was design to evaluate the inhibitory effects of JTE‐522 on rat colon tumorigenesis induced by 1,2‐dimethylhydrazine (DMH). Rats at 6 weeks of age were divided into 4 groups. One week after the start of the experiment, all rats received DMH by s.c. injection at a dose of 40 mg/kg body weight once a week for 4 successive weeks. As the initiation and postinitiation treatment groups, groups 1–3 were fed diets containing 0, 50, or 150 ppm JTE‐522, respectively, from the start of the study to the end. As the postinitiation treatment group, group 4 was given 150 ppm JTE‐522 from 1 week after the last DMH injection to the end of the study. Forty weeks after the start of the experiment, administration of 150 ppm JTE‐522 during both initiation and postinitiation stages significantly inhibited the incidences of tubular adenocarcinomas and total carcinomas, as well as total tumors in the colon. The inhibitory effect of JTE‐522 was most prominent for tubular adenocarcinomas, but was not observed in the nontubular carcinomas (signet‐ring cell and mucinous carcinomas). Almost equal inhibitory effects on tubular adenocarcinomas were also observed in the rats given 150 ppm JTE‐522 during the postinitiation stage, suggesting that its major anticancer action is at the postinitiation phase. However, JTE‐522 had no effect on the size or invasive extent of tubular adenocarcinomas. Furthermore, microarray analyses revealed that JTE‐522 had no effect on gene expression levels in DMH‐induced tubular adenocarcinomas. These findings suggest that JTE‐522 possesses chemopreventive activity against induction but not progression of tubular adenocarcinomas in rat colon. In view of the significant inhibitory effects of JTE‐522 on ACF, its major anticancer action may occur in the postinitiation stage but before the malignant conversion stage of DMH‐induced colon carcinogenesis.
Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma
Authors: Kwong Joseph , Lo Kwok‐Wai , Chow Lillian Shuk‐Nga , Chan Franky Leung , To Ka‐Fai , Huang Dolly P. 
Published: September 2004

AbstractTazarotene‐induced gene 1 (TIG1) and Tazarotene‐induced gene 3 (TIG3) are retinoid acid (RA) target genes as well as candidate tumor suppressor genes in human cancers. In our study, we have investigated the expression of TIG1 and TIG3 in nasopharyngeal carcinoma (NPC). Loss of TIG1 expression was found in 80% of NPC cell lines and 33% of xenografts, whereas TIG3 was expressed in all NPC samples and immortalized nasopharyngeal epithelial cells. In order to elucidate the epigenetic silencing of TIG1 in NPC, the methylation status of TIG1 promoter was examined by genomic bisulfite sequencing and methylation‐specific PCR (MSP). We have detected dense methylation of TIG1 5′CpG island in the 5 TIG1‐negative NPC cell lines and xenograft (C666‐1, CNE1, CNE2, HONE1 and X666). Partial methylation was observed in 1 NPC cell line HK1 showing dramatic decreased in TIG1 expression. Promoter methylation was absent in 2 TIG1‐expressed NPC xenografts and the normal epithelial cells. Restoration of TIG1 expression and unmethylated alleles were observed in NPC cell lines after 5‐aza‐2′‐deoxycytidine treatment. Moreover, the methylated TIG1 sequence was detected in 39 of 43 (90.7%) primary NPC tumors by MSP. In conclusion, our results showed that TIG1 expression is lost in the majority of NPC cell lines and xenografts, while promoter hypermethylation is the major mechanism for TIG1 silencing. Furthermore, the frequent epigenetic inactivation of TIG1 in primary NPC tumors implied that it may play an important role in NPC tumorigenesis.
Lower levels of nuclear β‐catenin predict for a poorer prognosis in localized prostate cancer
Authors: Horvath Lisa G. , Henshall Susan M. , Lee C.‐Soon , Kench James G. , Golovsky David , Brenner Phillip C. , O'Neill Gordon F. , Kooner Raji , Stricker Phillip D. , Grygiel John J. , Sutherland Robert L. 
Published: September 2004

Abstractβ‐catenin in its role as a nuclear signaling molecule has been implicated in prostate carcinogenesis primarily through modulation of androgen receptor activity. We defined the pattern of β‐catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and determined whether differences in expression were associated with disease progression and prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC) and 20 cases of advanced PC were assessed for β‐catenin expression using immunohistochemistry. Nuclear β‐catenin expression in localized PC was significantly lower than that in benign prostate tissue (p < 0.001) and significantly higher than that in advanced PC tissue (p < 0.001). In addition, lower levels of nuclear β‐catenin expression (< 10% of cancer cells) predicted for a shorter biochemical relapse‐free survival in patients with localized PC (p = 0.008) and were inversely correlated with preoperative prostate‐specific antigen (PSA) levels (p = 0.01). Analysis of the low‐risk subgroup of patients with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear β‐catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear β‐catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear β‐catenin expression is associated with a poorer prognosis in localized PC, in particular, in the low‐risk subgroup of patients with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear β‐catenin expression may be of clinical utility as a preoperative prognostic marker in low‐risk localized PC.
Cervical carcinoma in Algiers, Algeria: Human papillomavirus and lifestyle risk factors
Authors: Hammouda Doudja , Muñoz Nubia , Herrero Rolando , Arslan Annie , Bouhadef Anissa , Oublil Malika , Djedeat Belhout , Fontanière Bernard , Snijders Peter , Meijer Chris , Franceschi Silvia 
Published: September 2004

AbstractWe conducted a hospital‐based case‐control study in Algiers, Algeria. A total of 198 cervical carcinoma (CC) cases (including 15 adeno‐ and adenosquamous carcinomas) and 202 age‐matched control women were included. Human papillomavirus (HPV) DNA in cervical cells was evaluated using a PCR assay. Odds ratios and corresponding confidence intervals were computed by means of unconditional multiple logistic regression models. HPV infection was detected in 97.7% of CC cases and 12.4% of control women (OR = 635). Nineteen different HPV types were found. HPV 16 was the most common type in both CC cases and control women, followed by HPV 18 and 45. Twelve types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 66 and 73) were found as single infections in CC cases. Multiple HPV infections did not show a higher odds ratio for CC than single infections. In addition to HPV infection, husband's extramarital sexual relationships with other women (OR = 4.8) or prostitutes (OR = 3.2), residing in a rural environment for most of one's life (OR = 4.9) and indicators of poor sanitation or poor hygiene were the strongest risk factors for CC. Oral contraceptive use was unrelated to CC risk, while multiparity emerged as a significant risk factor after adjustment for sexual habits. Intrauterine device users showed a lower CC risk than nonusers. The role of major risk factors, except inside toilet, was confirmed in the analysis restricted to HPV‐positive women. The distribution of HPV types in CC cases and control women in Algeria is more similar to the one found in Europe than the one in sub‐Saharan Africa, where HPV 16 is less prevalent. A vaccine against HPV 16 and 18 may be effective in more than 3/4 of CCs in Algeria.
High throughput functional genomics: Identification of novel genes with tumor suppressor phenotypes
Authors: Koenig‐Hoffmann Kerstin , Bonin‐Debs Angelika L. , Boche Irene , Gawin Beate , Gnirke Andrea , Hergersberg Christoph , Madeo Frank , Kazinski Michael , Klein Matthias , Korherr Christian , Link Dieter , Röhrig Sascha , Schäfer Rolf , Brinkmann Ulrich 
Published: September 2004

AbstractWe have used a combination of high throughput functional genomics, computerized database mining and expression analyses to discover novel human tumor suppressor genes (TSGs). A genome‐wide high throughput cDNA phenotype screen was established to identify genes that induce apoptosis or reduce cell viability. TSGs are expressed in normal tissue and frequently act by reduction of growth of transformed cells or induce apoptosis. In agreement with that and thus serving as platform validation, our pro‐apoptotic hits included genes for which tumor suppressing activities were known, such as kangai1 and CD81 antigen. Additional genes that so far have been claimed as putative TSGs or associated with tumor inhibitory activities (prostate differentiation factor, hRAS‐like suppressor 3, DPH2L1‐like and the metastasis inhibitor Kiss1) were confirmed in their proposed TSG‐like phenotype by functionally defining their growth inhibitory or pro‐apoptotic function towards cancer cells. Finally, novel genes were identified for which neither association with cell growth nor with apoptosis were previously described. A subset of these genes show characteristics of TSGs because they (i) reduce the growth or induce apoptosis in tumor cells; (ii) show reduced expression in tumor vs. normal tissue; and (iii) are located on chromosomal (LOH‐) loci for which cancer‐associated deletions are described. The pro‐apoptotic phenotype and differential expression of these genes in normal and malignant tissue make them promising target candidates for the diagnosis and therapy of various tumors.
Differential expression of Protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples
Authors: Grisaru‐Granovsky Sorina , Salah Zaidoun , Maoz Myriam , Pruss Diana , Beller Uziel , Bar‐Shavit Rachel 
Published: September 2004

AbstractProtease activated receptors (PAR) form a family of G‐protein coupled receptors (GPCR) encoding their own ligands and uniquely activated via proteolytic cleavage. Although proteases in general have been implicated in the remodeling of the extracellular tumor microenvironment, the role of cell surface receptors activated by proteolysis is now emerging. In our present study we investigated the expression pattern of protease activated receptor 1 hPar1 in ovarian carcinoma tissue samples. Abundant hPar1 mRNA and protein were detected in “low malignant potential” and in invasive carcinomas, regardless of the histological subtype. In contrast, no hPar1 expression was detected on the cell surface of normal ovarian epithelium. The differential expression pattern of hPar1 was shown by in situ hybridization, immunohistochemistry and semi‐quantitative RT‐PCR analyses. In early stages of ovarian carcinoma (Ia), the contra lateral normal ovary showed strong PAR1 expression as opposed to the lack of expression in the ovarian epithelium obtained from normal individuals. In parallel, we analyzed the expression pattern of αvβ5 integrin and of activated focal adhesion kinase (FAK), a major focal contact protein, in these tissues. Although abundant expression of αvβ5 integrin was observed in all tissues specimens examined, regardless of either normal or malignant, the level of activated FAK was differentially expressed. Phosphorylated FAK was seen in invasive ovarian carcinoma, but not in the normal ovarian epithelium. The abundant hPar1 levels in pathological malignant ovarian carcinoma is likely to transmit signals leading to the phosphorylation of FAK and thereby alterations in the integrin functional state. Altogether our data suggest that hPar1 and FAK cooperate to promote ovarian cancer malignancy.
Hsp90 inhibitors deplete key anti‐apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin
Authors: Bagatell Rochelle , Beliakoff Jason , David Cynthia L. , Marron Marilyn T. , Whitesell Luke 
Published: September 2004

AbstractDrugs that inhibit the function of heat shock protein 90 (Hsp90) are of interest in the treatment of pediatric cancers because these agents deplete the cellular levels of signaling molecules that are important for the growth and survival of many childhood tumors. To generate preclinical data in anticipation of clinical trials of Hsp90 inhibitors in children, we evaluated the effects of the Hsp90 inhibitor geldanamycin (GA) alone and in combination with cis‐platinum (II)‐diamine dichloride (cisplatin) in pediatric tumor cells. Immunoblotting demonstrated depletion of the Hsp90 client proteins AKT and the type 1 insulin‐like growth factor receptor (IGF1R) in a panel of pediatric tumor cell lines after exposure to GA. Drug exposure also led to a dramatic decrease in cell survival/proliferation in MYCN‐amplified and non‐amplified neuroblastoma cells. Moderate inhibition of survival/proliferation was observed in RB‐deficient and wild‐type osteosarcoma cells. Treatment of neuroblastoma and osteosarcoma cell lines with GA in combination with cisplatin resulted in greater than additive inhibition of survival/proliferation based on median dose analysis. Exposure to this drug combination also resulted in a marked increase in nuclear fragmentation as assessed by terminal deoxynucleotide transferase‐mediated UTP nick end labeling (TUNEL) analysis. Combined exposure also abrogated the ability of GA to induce a cytoprotective heat shock response and resulted in Hsp90 adduct formation. Our findings suggest that Hsp90 inhibitors may prove useful either alone or as a component of multi‐drug regimens in the treatment of neuroblastoma and osteosarcoma.
The asymmetric effects of uncertainty on inflation and output growth
Authors: Grier Kevin B. , Henry Ólan T. , Olekalns Nilss , Shields Kalvinder 
Published: September 2004

AbstractWe study the effects of growth volatility and inflation volatility on average rates of output growth and inflation for post‐war US data. Our results suggest that increased growth uncertainty is associated with significantly lower average growth, while higher inflation uncertainty is significantly negatively correlated with lower output growth and lower average inflation. Both inflation and growth display evidence of significant asymmetric response to positive and negative shocks of equal magnitude. Copyright © 2004 John Wiley & Sons, Ltd.
Interferon‐α and antisense K‐ras RNA combination gene therapy against pancreatic cancer
Authors: Hatanaka Kazuteru , Suzuki Koichi , Miura Yoshiaki , Yoshida Kimiko , Ohnami Shumpei , Kitade Yukio , Yoshida Teruhiko , Aoki Kazunori 
Published: September 2004

AbstractInterferon alpha (IFN‐α) is used worldwide for the treatment of a variety of cancers. For pancreatic cancer, recent clinical trials using IFN‐α in combination with standard chemotherapeutic drugs showed some antitumor activity of the cytokine, but the effect was not significant enough to enlist pancreatic cancer as a clinically effective target of IFN‐α. In general, an improved therapeutic effect and safety are expected for cytokine therapy when given in a gene therapy context, because the technology would allow increased local concentrations of this cytokine in the target sites. In this study, we first examined the antiproliferative effect of IFN‐α gene transduction into pancreatic cancer cells. The expression of IFN‐α effectively induced growth suppression and cell death in pancreatic cancer cells, an effect which appeared to be more prominent when compared with other types of cancers and normal cells. Another strategy we have been developing for pancreatic cancer targets its characteristic genetic aberration, K‐ras point mutation, and we reported that the expression of antisense K‐ras RNA significantly suppressed the growth of pancreatic cancer cells. When these two gene therapy strategies are combined, the expression of antisense K‐ras RNA significantly enhanced IFN‐α‐induced cell death (1.3‐ to 3.5‐fold), and suppressed subcutaneous growth of pancreatic cancer cells in mice. Because the 2′,5′‐oligoadenylate synthetase/RNase L pathway, which is regulated by IFN and induces apoptosis of cells, is activated by double‐strand RNA, it is plausible that the double‐strand RNA formed by antisene and endogeneous K‐ras RNA enhanced the antitumor activity of IFN‐α. This study suggested that the combination of IFN‐α and antisense K‐ras RNA is a promising gene therapy strategy against pancreatic cancer. Copyright © 2004 John Wiley & Sons, Ltd.