bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: Diagnostic and prognostic implications
Authors: Jung Klaus , Lein Michael , Stephan Carsten , Von Hösslin Katharina , Semjonow Axel , Sinha Pranav , Loening Stefan A. , Schnorr Dietmar 
Published: May 2004

AbstractOur aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa‐caused mortality. In sera of 117 PCa patients (pN0M0, n = 39; pN1M0, n = 34; M1, n = 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone‐specific alkaline phosphatase (tALP, bALP), amino‐terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC)], bone resorption markers [bone sialoprotein (BSP), cross‐linked C‐terminal (CTX) and cross‐linked N‐terminal (NTX) telopeptides of type I collagen, tartrate‐resistant acid phosphatase isoenzyme 5b (TRAP)] and osteoclastogenesis markers [osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL)] were measured. tALP, bALP, BSP, P1NP, TRAP, NTX and OPG were significantly increased in PCa patients with bone metastases compared to patients without metastases. OPG showed the best discriminatory power to differentiate between these patients. Logistic regression analysis resulted in a model with OPG and TRAP as variables that predicted bone metastasis with an overall correct classification of 93%. Patients with concentrations of OPG, P1NP, tALP, bALP, BSP, NTX, TRAP and CTX above cut‐off levels showed significantly shorter survival than patients with low marker concentrations. Multivariate Cox proportional hazards regression revealed that only OPG and BSP were independent prognostic factors for PCa‐related death. Thus, the importance of serum OPG in detecting bone metastatic spread, alone or in combination with other bone markers, and predicting survival in PCa patients has been clearly demonstrated. © 2004 Wiley‐Liss, Inc.
Neoexpression of N‐cadherin in E‐cadherin positive colon cancers
Authors: Rosivatz Erika , Becker Ingrid , Bamba Masamichi , Schott Christina , Diebold Joachim , Mayr Doris , Höfler Heinz , Becker Karl‐Friedrich 
Published: May 2004

AbstractIn our study, we aimed to investigate the expression of N‐cadherin and E‐cadherin and their dependency on epithelial‐mesenchymal transition regulators SNAI1, SIP1 and TWIST in human colon cancer. Expression of E‐cadherin and N‐cadherin was examined by immunohistochemistry in 80 colon carcinomas by using paraffin embedded and formalin fixed tissues. Those cases were partly analyzed for mRNA expression of N‐cadherin (42 cases), TWIST (18 cases), SNAI1 (25 cases) and SIP1 (25 cases) by real‐time quantitative RT‐PCR. Additionally, colon carcinomas that showed amplification of 20q13, the localization of the human SNAI1 gene, were examined. We found cytoplasmic and/or membrane‐associated immunoreactivity of N‐cadherin in 35/80 (44%) of the cases. However, there was no correlation to upregulated TWIST mRNA levels, as we have shown previously for diffuse‐type gastric cancers with abnormal N‐cadherin expression. Reduced and/or cytoplasmic E‐cadherin immunoreactivity was detected in 19% (15/80) of the cases. Expression of SNAI1 or SIP1 mRNA was not seen in any of the 25 cases analyzed. There was no correlation between amplification of 20q13 and SNAI1 mRNA expression. Remarkably, N‐cadherin was almost exclusively expressed in those cases showing normal E‐cadherin immunoreactivity, suggesting a mutual exclusion between abnormal E‐cadherin reduction and upregulation of N‐cadherin. For the first time, we postulate a role for N‐cadherin in primary colon cancer progression, which may be similar to the effect discovered by others in breast cancer cell lines, where coexpressed N‐cadherin can exert a dominant function over E‐cadherin's adhesive function and thus promote tumor invasiveness. © 2004 Wiley‐Liss, Inc.
Preoperative hCGβ and CA 72‐4 are prognostic factors in gastric cancer
Authors: Louhimo Johanna , Kokkola Arto , Alfthan Henrik , Stenman Ulf‐Håkan , Haglund Caj 
Published: May 2004

AbstractIn gastric cancer, the role of tumour markers in assessment of prognosis is unconfirmed. In our study, we evaluated the prognostic significance of serum tumour markers carcinoembryonic antigen (CEA), CA 19‐9, CA 72‐4, CA 242 and free β subunit of human chorionic gonadotropin (hCGβ) in gastric cancer. Preoperative serum samples were obtained from 146 patients with gastric cancer, including 29 with stage I, 11 with stage II, 42 with stage III and 64 patients with stage IV cancer. Quantitation of CEA, CA 19‐9, CA 72‐4 and CA 242 in serum was performed with commercial assays. HCGβ was measured with an in‐house immunofluorometric assay based on monoclonal antibodies specific for the free β‐subunit of hCG. Survival analysis was performed with Kaplan‐Meier life‐tables and log‐rank test, and with multivariate Cox regression analysis. Disease‐specific cumulative 2‐year survival rate was 40%. Serum levels of CEA, CA 72‐4, CA 242 and hCGβ showed significant correlation with stage (p<0.027); for CA 19‐9 the association was of borderline significance (p=0.056). Of the studied markers, CA 19‐9, CA 72‐4, CA 242 and hCGβ were found to be prognostic factors in univariate analysis (p< 0.022). In multivariate analysis, stage had the statistically most significant association with prognosis followed by hCGβ, tumour histology according to the Laurén classification and by CA 72‐4. In gastric cancer, tumour markers hCGβ and CA 72‐4 are independent prognostic factors in addition to stage and histological type of the tumour. © 2004 Wiley‐Liss, Inc.
Association between female breast cancer and cutaneous melanoma
Authors: Goggins William , Gao Wei , Tsao Hensin 
Published: May 2004

AbstractEpidemiologic studies have provided suggestive evidence of a link between cutaneous melanoma (CM) and breast cancer (BC). Moreover, carriers of mutations in the breast cancer predisposition gene, BRCA2, have an increased risk of melanoma while carriers of mutations in the melanoma susceptibility gene, CDKN2A, exhibit a higher than expected risk of breast cancer. These findings raise the possibility that pathways involved in the development of CM and BC overlap and that survivors of one cancer may be prone to develop the other. To this end, we set out to determine if survivors of female BC in the Surveillance, Epidemiology and End Result (SEER) database are at increased risk for CM and vice versa. We followed female BC patients registered in the 1973—1999 SEER database for development of a second CM and female CM patients for the development of a second BC. The expected number of cases was then compared to the observed number of cases using standardized incidence ratios. Overall, we found a modest but statistically significant increased risk of CM among female BC survivors and vice versa. Among young BC patients, we observed a 46% elevated risk of a second CM. Women who underwent radiation therapy exhibited a 42% increased risk for CM. The risks of BC among female CM survivors and CM among BC survivors were also elevated, albeit to a much lesser degree (overall, 11% and 16%, respectively). We found a mutual association between female BC and CM. The elevated risk for CM, especially among younger BC patients, suggests that the genetic observations from high‐risk groups may also be operative at a much lower level in the general BC population. © 2004 Wiley‐Liss, Inc.
DNA binding sites for putative methylation boundaries in the unmethylated region of the BRCA1 promoter
Authors: Butcher Darci T. , Mancini‐DiNardo Debora N. , Archer Trevor K. , Rodenhiser David I. 
Published: May 2004

AbstractChanges in DNA methylation patterns are frequently observed in human cancers and are associated with a decrease in tumor suppressor gene expression. Hypermethylation of the BRCA1 promoter has been reported in a portion of sporadic breast tumours that correspond to a reduction in BRCA1 transcription and expression. Questions remain concerning the maintenance of methylation free zones in promoter regions of tumor suppressor genes in normal tissues. Sodium bisulfite based analysis of the BRCA1 promoter defines a methylation free zone in normal breast tissue that starts 650 bp upstream of the transcription start site and extends for 1.4 kb through most of the BRCA1 CpG island. We provide data implicating 2 proteins, Sp1 and CTCF, in the maintenance of this methylation‐free zone. Both of these proteins have been shown to function as methylation boundaries in other genes. Four Sp1 sites have been identified in the BRCA1 promoter by gel shift assays. In vivo binding of Sp1 has been confirmed at 2 of these sites in the BRCA1 promoter and at 2 CTCF sites that flank the unmethylated region. Our data suggest that these DNA binding sites for Sp1 and CTCF may act as boundary elements that are important in maintaining genomic integrity by delineating the normal methylation free BRCA1 promoter. Inactivation or disruption of these boundaries may facilitate an epigenetic “hit”, in this case DNA methylation, leading to BRCA1 downregulation and contributing to tumorigenesis, particularly the genesis of sporadic breast tumours. © 2004 Wiley‐Liss, Inc.
Dietary calcium, vitamin D, VDR genotypes and colorectal cancer
Authors: Slattery Martha L. , Neuhausen Susan L. , Hoffman Michael , Caan Bette , Curtin Karen , Ma Khe Ni , Samowitz Wade 
Published: May 2004

AbstractThe vitamin D receptor (VDR) may importantly modulate risk of colorectal cancer either independently or in conjunction with calcium and vitamin D intake. We evaluate the association between calcium, vitamin D, dairy products, and VDR polymorphisms in 2 case‐control studies of colon and rectal cancer (n = 2,306 cases and 2,749 controls). Dietary intake was evaluated using a detailed diet history questionnaire. Two VDR polymorphisms were evaluated: an intron 8 Bsm 1 polymorphism and a 3′ untranslated region poly‐A length polymorphism (designated S for short and L for long). The SS genotype reduced risk of colorectal cancer for men (odds ratio [OR] = 0.71; 95% confidence interval [CI] = 0.55–0.92). High levels of calcium intake reduced risk of rectal cancer in women (OR = 0.39; 95% CI = 0.24–0.64) but were not associated with rectal cancer in men (OR = 1.02; 95% CI = 0.66–1.56). Similar reduced rectal cancer risk among women was observed at high levels of vitamin D (OR = 0.52; 95% CI = 0.32–0.85) and low‐fat dairy products (OR = 0.61; 95% CI = 0.39–0.94). High levels of sunshine exposure reduced risk of rectal cancer among those diagnosed when <60 years of age (OR = 0.62, 95% CI = 0.42–0.93). Examination of calcium in conjunction with VDR genotype showed that a significant 40% reduction in risk of rectal cancer was observed for the SS or BB VDR genotypes when calcium intake was low (p interaction = 0.01 for calcium interaction). For colon cancer, high levels of dietary intake of calcium, vitamin D, and low‐fat dairy products reduced risk of cancer for the SS or BB VDR genotypes, although the p for interaction was not statistically significant. These data support previous observations that high levels of calcium and vitamin D reduce risk of rectal cancer and provide support for a weak protective effect for the SS and BB VDR genotypes. The risk associated with VDR genotype seems to depend upon the level of dietary calcium and vitamin D and tumor site. © 2004 Wiley‐Liss, Inc.
Vaccination with tumor cell lysate‐pulsed dendritic cells augments the effect of IFN‐β gene therapy for malignant glioma in an experimental mouse intracranial glioma
Authors: Saito Ryuta , Mizuno Masaaki , Nakahara Norimoto , Tsuno Takaya , Kumabe Toshihiro , Yoshimoto Takashi , Yoshida Jun 
Published: May 2004

AbstractInterferon‐β (IFN‐β) has been used as an antitumor drug against human glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a new gene therapy using the IFN‐β gene against malignant gliomas and then began clinical trials in 2000. Since stimulation of immune system was one mechanism of antitumor effect induced by IFN‐β gene therapy, we hypothesized that combination of IFN‐β gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN‐β gene therapy and immunotherapy using tumor cell lysate‐pulsed dendritic cells (DCs) would increase the efficacy of IFN‐β gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN‐β gene therapy or DC immunotherapy alone, IFN‐β gene therapy following DC immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future. © 2004 Wiley‐Liss, Inc.
Extensive analysis of the 7q31 region in human prostate tumors supports TES as the best candidate tumor suppressor gene
Authors: Chêne Laurent , Giroud Christiane , Desgrandchamps François , Boccon‐Gibod Laurent , Cussenot Olivier , Berthon Philippe , Latil Alain 
Published: May 2004

AbstractLoss of heterozygosity (LOH) on chromosome arm 7q31 is found in many prostate tumors. Such alterations are generally associated with inactivation of tumor suppressor genes. It has been shown previously that the main region of LOH at 7q31 spans the interval between the D7S486 and D7S2460 microsatellite loci, which contains several candidate tumor suppressor genes (TSG) such as TES, CAV2, CAV1, MET, CAPZA2, ST7 and WNT2. We tested 41 human sporadic prostate tumors for 7q31 LOH by using 5 polymorphic markers overlapping the critical region and used a real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay to study the expression of the 7 candidate TSGs located in this genomic region. We found that CAV1, CAV2, MET and TES mRNA expression was lower in prostate tumors than in normal prostate tissues. Our immunohistochemical results and previously published data on the compartmental expression of these messenger RNAs in stromal and epithelial cells suggest that TES is the best candidate tumor suppressor gene at 7q31. © 2004 Wiley‐Liss, Inc.
Possible association between HPV16 E7 protein level and cytokeratin 19
Authors: Favia Gianfranco , Kanduc Darja , Lo Muzio Lorenzo , Lucchese Alberta , Serpico Rosario 
Published: May 2004

AbstractThe mechanisms employed by human papillomaviruses (HPVs) to control the replication of the viral genome and the expression of the viral genes are extremely complex and further complicated by the fact that the viral life cycle is intricately tied to the differentiation program of its host epithelial tissue. Indeed, HPV‐induced immortalization of keratinocytes and disruption of the normal cytokeratin (CK) expression pattern progress pari passu during the stepwise process that preludes to squamous cell carcinoma. In our study, we have analyzed the interaction occurring between HPV type 16 E7 mRNA and the intermediate cytokeratin filaments 7 and 19 and report data in favor of a possible association between HPV16 E7 protein level and CK19. © 2004 Wiley‐Liss, Inc.
Genetic epidemiology of cancer: From families to heritable genes
Authors: Hemminki Kari , Rawal Rajesh , Chen Bowang , Bermejo Justo Lorenzo 
Published: May 2004

AbstractA reliable determination of familial risks for cancer is important for clinical counseling, prevention and understanding cancer etiology. Family‐based gene identification efforts may be targeted if the risks are well characterized and the mode of inheritance is identified. Medically verified data on familial risks have not been available for all types of cancer but they have become available through the use of the nationwide Swedish Family‐Cancer Database, which includes all Swedes born in 1932 and later with their parents, totaling over 10 million individuals. Over 150 publications have emanated from this source. The familial risks of cancer have been characterized for all main cancers and the contribution of environmental and heritable effects to the familial aggregation has been assessed. Furthermore, the mode of inheritance has been deduced by comparing risks from parental and sibling probands. Examples are shown on familial clustering of cancers, for which heritable susceptibility genes are yet unknown, such as squamous cell carcinoma of the skin, intestinal carcinoids, thyroid papillary tumors, brain astrocytomas and pituitary adenomas. Some common cancers, such as lung and kidney cancers, appear to show an early‐onset recessive component because familial risks among siblings are much higher than those in families where parents are probands. Many of the cancer sites showing high familial risks lack guidelines for clinical counseling or action level. In conclusion, we recommend that any future gene identification efforts, either using linkage or association designs, devise their strategies based on data from family studies. Clinical genetic counseling would benefit from reviewing established familial risks on all main types of cancer. © 2004 Wiley‐Liss, Inc.
Downregulation of KiSS‐1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma
Authors: Dhar Dipok Kumar , Naora Hiroyuki , Kubota Hirofumi , Maruyama Riruke , Yoshimura Hiroshi , Tonomoto Yasuhito , Tachibana Mitsuo , Ono Takashi , Otani Hiroki , Nagasue Naofumi 
Published: May 2004

AbstractKiSS‐1 is a promising candidate tumor‐suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS‐1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS‐1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS‐1 expression by using the median as the cutoff value of KiSS‐1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS‐1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS‐1‐expressing tumors had a significantly worse overall and disease‐free survival. In multivariate analysis, KiSS‐1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS‐1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention. © 2004 Wiley‐Liss, Inc.
ZNF143 activates gene expression in response to DNA damage and binds to cisplatin‐modified DNA
Authors: Ishiguchi Hiroshi , Izumi Hiroto , Torigoe Takayuki , Yoshida Yoichiro , Kubota Hiroshi , Tsuji Sadatoshi , Kohno Kimitoshi 
Published: May 2004

AbstractWe have identified a cisplatin‐inducible gene, the mitochondrial ribosomal protein S11 (MRP S11) gene, by means of mRNA differential display. Functional analysis of the MRP S11 promoter showed that a Staf binding site in the promoter is required for both basal promoter activity and cisplatin‐inducible activity. We also found that Staf binding activity is significantly increased in nuclear extracts from cells treated with cisplatin. ZNF 143 and ZNF 76 are human homologues of the Xenopus transcriptional activator, Staf. ZNF 143 expression is induced by cisplatin but ZNF 76 expression is not. However, ZNF 143 expression is not induced by transplatin, which is clinically ineffective. ZNF143 is an inducible gene by other DNA damaging agents such as γ‐irradiation, etoposide and adriamycin. ZNF 143 also binds preferentially to cisplatin‐modified DNA. These results suggest that ZNF 143 participates in cellular responses to DNA damage. © 2004 Wiley‐Liss, Inc.
Pegylated polystyrene particles as a model system for artificial cells
Authors: Meng Fenghua , Engbers Gerard H. M. , Gessner Andrea , Müller Reiner H. , Feijen Jan 
Published: May 2004

AbstractPegylated polystyrene particles (PS‐PEG) were prepared as a model system for artificial cells, by modification of carboxyl polystyrene particles (PS‐COOH) with homo‐ and hetero‐bifunctional polyethylene glycols (PEG, MW 1500, 3400, and 5000) containing an amino end group for immobilization and an amino, hydroxyl, or methoxy end group that is exposed at the surface after immobilization. Protein adsorption from human plasma dilutions (85 v %) onto PS‐PEG with a PEG surface concentration higher than 40 pmol/cm2 was reduced up to 90–95% compared with protein adsorption onto PS‐COOH with a final protein surface concentration of ∼30 ng/cm2. Two‐dimensional gel electrophoresis analyses showed that 30% of the total amount of adsorbed proteins onto PS‐PEG are dysopsonins (i.e., nonadhesive proteins like albumin and apolipoproteins). For PS‐COOH, <15% of the amount of adsorbed proteins are dysopsonins. In addition, the generation of terminal complement compound (TCC) by PS‐PEG particles with a PEG surface concentration lower than ∼55 pmol/cm2 is not significant. The low protein adsorption, the relatively high percentage of adsorbed dysopsonins, and the low level of complement activation may prevent the uptake of PS‐PEG by the mononuclear phagocytic system (MPS) in vivo. Moreover, PS‐PEG (PEG surface concentration > ∼35 pmol/cm2) shows minimal interaction with cultured human umbilical vein endothelial cells (HUVEC), which mimics the endothelial lining of the blood vessel wall. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 97–106, 2004
PLA and PLGA microspheres of β‐galactosidase: Effect of formulation factors on protein antigenicity and immunogenicity
Authors: Stivaktakis N. , Nikou K. , Panagi Z. , Beletsi A. , Leondiadis L. , Avgoustakis K. 
Published: May 2004

AbstractThe entrapment of β‐galactosidase (Escherichia coli) in PLA and PLGA microspheres using a double emulsion technique resulted to significant reduction of protein antigenicity. The extent of antigenicity loss depended on the conditions of microsphere preparation. Most of antigenicity loss occurred on the first emulsification step. Only the effects of microsphere preparation factors having an important influence on protein antigenicity, such as the type of organic phase (polymer solvent) and homogenization, could be predicted (on a qualitative basis) by antigenicity data obtained after the first emulsification step. The type of polymer and polymer solvent used to prepare the microspheres affected β‐galactosidase immunogenicity. The PLA microspheres prepared using ethyl acetate was the most immunogenic microsphere formulation, eliciting similar total antibody responses as the alum formulation of β‐gal. This formulation was the only microsphere formulation that induced an IgG1/IgG2a ratio lower than 1, indicating an immune response biased towards a Th1 type. The results obtained indicate that large protein molecules with complex tertiary structure such as β‐galactosidase can be entrapped in PLA and PLGA microspheres with retention of protein immunogenic potential, providing that appropriate conditions of microsphere preparation are applied, and that the formulation of microspheres might influence the Th1/Th2 type of immune response against the encapsulated antigen. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 139–148, 2004