bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective occlusion of tumor blood vessels by targeted delivery of an antibody‐photosensitizer conjugate
Authors: Fabbrini Monica , Trachsel Eveline , Soldani Patrizia , Bindi Stefano , Alessi Patrizia , Bracci Luisa , Kosmehl Hartwig , Zardi Luciano , Neri Dario , Neri Paolo 
Published: October 2005

AbstractThe irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e6, after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody‐photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis‐related pathologies. © 2005 Wiley‐Liss, Inc.
HER2amplification in recurrent breast cancer following breast‐conserving therapy correlates with distant metastasis and poor survival
Authors: López‐Guerrero José A. , Llombart‐Cussac Antonio , Noguera Rosa , Navarro Samuel , Pellin Antonio , Almenar Sergio , Vazquez‐Alvadalejo Carlos , Llombart‐Bosch Antonio 
Published: October 2005

AbstractThe authors analyzed theHER2status in early‐stage nonrecurrent and recurrent breast cancer groups following breast‐conserving treatment. Retrospective analyses of a group of 36 invasive early breast cancer (IBC) patients who developed a local recurrence as a first event and of a random control group of 69 IBC patients were made.HER2status was assessed by the HercepTest® (Dako Corp., Carpinteria, CA) and fluorescencein situhybridization. The Kaplan–Meier proportional log‐rank test was used to study the impact of the biological factors on the metastasis‐free interval (MFI) and the overall survival (OS). The Cox proportional hazards model, using stepwise selection was performed to identify the independent predictors of poor outcome. The median time of follow‐up was 156 months (range: 22–230) for the nonrecurrent group of patients and 119 months (range: 36–228) for the recurrent group. No significant differences between either group were observed in terms of either patient or tumor characteristics, or of HER2 expression. However, a higher proportion ofHER2amplified cases were found in the recurrent group, in contrast to a higher proportion of hormonal receptor positive cases in the nonrecurrent group. After univariate and multivariate analyses,HER2amplification was found to be an independent predictive factor for distant metastasis (HR = 10.75;p= 0.00008) and for survival (HR = 4.22;p= 0.004). In conclusion,HER2amplification constitutes an independent poor prognostic factor for the MFI and OS in patients with recurrent breast cancer. The clinical implications are discussed. © 2005 Wiley‐Liss, Inc.
Exploring SNP‐SNP interactions and colon cancer risk using polymorphism interaction analysis
Authors: Goodman Julie E. , Mechanic Leah E. , Luke Brian T. , Ambs Stefan , Chanock Stephen , Harris Curtis C. 
Published: October 2005

AbstractSeveral single nucleotide polymorphisms (SNPs) in genes derived from distinct pathways are associated with colon cancer risk; however, few studies have examined SNP‐SNP interactions concurrently. We explored the association between colon cancer and 94 SNPs, using a novel approach, polymorphism interaction analysis (PIA). We developed PIA to examine all possible SNP combinations, based on the 94 SNPs studied in 216 male colon cancer cases and 255 male controls, employing 2 separate functions that crossvalidate and minimize false‐positive results in the evaluation of SNP combinations to predict colon cancer risk. PIA identified previously described null polymorphisms in glutathione‐S‐transferase T1 (GSTT1) as the best predictor of colon cancer among the studied SNPs, and also identified novel polymorphisms in the inflammation and hormone metabolism pathways that singly or jointly predict cancer risk. PIA identified SNPs that may interact with the GSTT1 polymorphism, including coding polymorphisms in TP53 (Arg72Pro in p53) and CASP8 (Asp302His in caspase 8), which may modify the association between this polymorphism and colon cancer. This was confirmed by logistic regression, as the GSTT1 null polymorphism in combination with either the TP53 or the CASP8 polymorphism significantly alter colon cancer risk (pinteraction < 0.02 for both). GSTT1 prevents DNA damage by detoxifying mutagenic compounds, while the p53 protein facilitates repair of DNA damage and induces apoptosis, and caspase 8 is activated in p53‐mediated apoptosis. Our results suggest that PIA is a valid method for suggesting SNP‐SNP interactions that may be validated in future studies, using more traditional statistical methods on different datasets (Supplementary material can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat). Published 2005 Wiley‐Liss, Inc.
Selenium supplementation and colorectal adenomas: An analysis of the nutritional prevention of cancer trial
Authors: Reid Mary E. , Duffield‐Lillico Anna J. , Sunga Annette , Fakih Marwan , Alberts David S. , Marshall James R. 
Published: October 2005

AbstractSelenium status has been inversely associated with colorectal cancers (CRC) and adenomas. This investigation evaluates the association between selenium supplementation and prevalent and incident colorectal adenomas and CRC detected during the Nutritional Prevention of Cancer trial follow‐up. Of the 1,312 randomized to 200 mcg of selenized yeast of matching placebo, 598 participants underwent endoscopic screening (flexible sigmoidoscopy or colonoscopy) for CRC sometime during the follow‐up period, which ended in February 1, 1996. There was no colorectal screening performed at baseline. Of those screened, 77% were male (with a mean age of 62.8 years), 42% were former and 25% were current smokers. Adenomas were classified as prevalent (identified at the first endoscopic examination postrandomization during the follow‐up period) or incident (identified at the second or subsequent examination). Ninety‐nine prevalent and 61 incident adenomas were ascertained. Logistic regression odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender and smoking status. For prevalent adenomas, there was a suggestive but nonsignificant decrease in risk associated with selenium treatment (OR = 0.67, 95% CI = 0.43–1.05). Subjects in the lowest tertile of baseline selenium (OR = 0.27, 95% CI = 0.09–0.77) and current smokers (OR = 0.27, 95% CI = 0.11–0.66) had significant reductions in risk. The OR for incident adenomas was 0.98 (95% CI = 0.57–1.68). In addition to being associated with a reduced risk of incident CRC, selenium supplementation was associated with a significantly reduced risk of prevalent adenomas, but only among subjects with either a low baseline selenium level or among current smokers. © 2005 Wiley‐Liss, Inc.
Association of a distinctive strain of Epstein‐Barr virus with gastric cancer
Authors: Corvalan Alejandro , Ding Shan , Koriyama Chihaya , Carrascal Edwin , Carrasquilla Gabriel , Backhouse Claudia , Urzua Luz , Argandoña Jorge , Palma Mariana , Eizuru Yoshito , Akiba Suminori 
Published: October 2005

AbstractEpstein‐Barr virus (EBV) has been linked to gastric carcinoma (GC) with worldwide geographical variations attributable to types and variants of EBV. Here, we compare EBV strains between EBVaGC and healthy donors in Latin America, a high frequency area for EBVaGC. Tumor samples from 73 EBVaGC cases and throat washings from 329 healthy adults were examined for types 1 and 2 EBV and polymorphism at BamHI‐F and BamHI‐W1/I1 boundary regions and XhoI restriction site in LMP1 gene. Type 1 and prototype F of BamHI‐ F polymorphism accounted 59 (81%) and 69 (95%) of EBVaGC cases and 257 (78%) and 267 (81%) of healthy donors, respectively. Types I and “i” of BamHI W1/I1 polymorphism accounted 2 (3%) and 62 (85%) of EBVaGC and 85 (26%) and 170 (52%) of healthy donors, respectively (p<0.001). XhoI+ and − polymorphism accounted 60 (82%) and 4 (5%) of EBVaGC and 142 (43%) and 92 (28%) of healthy donors, respectively (p<0.001). Cosegregation analysis demonstrated that most of the 62 type “i” EBVaGC cases harbor XhoI+ strain (81%). However, among 143 type “i” healthy adults, both XhoI polymorphism were present in relatively similar frequencies (XhoI+ 58% and XhoI− 42%) (OR 9.0; 95% CI 1.2–69). Our findings are against to the proposed hypothesis that EBV strains are geographically but not disease‐restricted. We conclude that most of the EBVaGC cases harbor a distinctive EBV strain (type “i”/XhoI +), but in healthy donors, this strain was as common as other strains. This finding is contrary to the proposed hypothesis that EBV strains are geographically but not disease‐restricted and identified a healthy population group that share the same strain that predominate in EBVaGC cases. © 2005 Wiley‐Liss, Inc.
Immune stimulatory effects of CD70 override CD70‐mediated immune cell apoptosis in rodent glioma models and confer long‐lasting antiglioma immunity in vivo
Authors: Aulwurm Steffen , Wischhusen Jörg , Friese Manuel , Borst Jannie , Weller Michael 
Published: October 2005

AbstractCD70 (CD27 ligand) promotes the expansion of primed lymphocytes by enhancing cell survival. Surprisingly, we previously observed that CD70 aberrantly expressed on human glioma cells promoted immune cell apoptosis and inhibited alloreactive lysis. Here we report that ectopic expression of CD70 in mouse glioma cells enhances apoptosis of T, B and NK cells in coculture, but nevertheless promotes glioma cell lysis by NK cells in vitro. In nude mice, CD70 expression in SMA‐560 gliomas delays the glioma growth upon subcutaneous (s.c.) or intracerebral (i.c.) inoculation, suggesting a role for CD70/CD27‐dependent NK cell activity in tumor surveillance. In syngeneic immunocompetent VM/Dk mice, CD70 allows the rejection of s.c. and i.c. implanted SMA‐560 tumors. The tumorigenicity of CD70‐expressing glioma cells is abrogated when TGF‐β signaling is blocked. Moreover, mice surviving the s.c. CD70 glioma challenge subsequently also reject wild‐type glioma cells administered i.c. Similarly, CD70‐expressing GL‐261 gliomas are rejected in syngeneic C57BL/6 mice, while glioma growth is restored in C57BL/6 CD27−/− mice, suggesting that the CD70/CD27 interaction recruits a tumor‐specific T‐cell repertoire and induces tumor‐specific memory. Altogether, these observations indicate that the net effect of aberrant CD70 expression in gliomas is immune stimulatory rather than immune paralytic and encourage its application in tumor immunotherapy. © 2005 Wiley‐Liss, Inc.
Green tea catechin, epigallocatechin‐3‐gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex
Authors: Rodriguez Shaun K. , Guo Weimin , Liu Liping , Band Michael A. , Paulson Eric K. , Meydani Mohsen 
Published: October 2005

AbstractA potential mechanism by which green tea may prevent cancer development is through the inhibition of angiogenesis. We have shown previously that the green tea catechin, epigallocatechin gallate (EGCG), inhibits endothelial cell tube formation through the inhibition of vascular endothelial growth factor (VEGF)‐induced Akt activation and vascular endothelial (VE)‐cadherin phosphorylation. Furthermore, EGCG can suppress oxidant‐induced production of the proangiogenic cytokine interleukin (IL)‐8. To further elucidate the antiangiogenic mechanisms of EGCG, we investigated its regulation of other molecular processes in VEGF‐induced signaling in human umbilical vein endothelial cells (HUVECs). We show that EGCG at physiological doses (0.5–10 μM) markedly inhibits the formation of a vascular endothelial growth factor receptor 2 complex formed upon the binding of its ligand VEGF. This disruption results in a significant and dose‐dependent decrease in PI3‐kinase activity. Electrophoretic mobility shift assay revealed that EGCG decreased the PI3 kinase‐dependent activation and DNA‐binding ability of NF‐κB, likely acting through decreasing phosphorylation and degradation of IκB. VEGF‐induced IL‐8 production at the mRNA (real time RT‐PCR) and protein levels (ELISA) are also suppressed with EGCG. These results suggest a novel mechanism for green tea's anticancer effects where EGCG can abrogate VEGF signaling by interfering with the formation of a receptor complex, resulting in attenuated mitogenic and angiogenic signaling. © 2005 Wiley‐Liss, Inc.
Identification of a novel human tissue factor splice variant that is upregulated in tumor cells
Authors: Chand Hitendra S. , Ness Scott A. , Kisiel Walter 
Published: October 2005

AbstractTissue factor (TF) is a transmembrane glycoprotein that serves as the prime initiator of blood coagulation and plays a critical role in thrombosis and hemostasis. In addition, a variety of tumor cells overexpress cell‐surface TF, which appears to be important for tumor angiogenesis and metastasis. To elucidate the mechanism involved in the upregulation of TF in human tumor cells, a comprehensive analysis of TF mRNA from various normal and tumor cells was performed. The results of these studies indicate that, in addition to possessing a normal full‐length TF transcript and minor levels of an alternatively spliced transcript known as alternatively‐spliced tissue factor (asTF) (Bogdanov et al., Nat Med 2003;9:458–62), human tumor cells express additional full‐length TF transcripts that are also generated by alternative splicing. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and 5′‐rapid amplification of cDNA ends‐ (5′‐RACE) based analyses of cytoplasmic RNA from normal and tumor cells revealed that there is alternative splicing of the first intron between exon I and exon II resulting in 2 additional TF transcripts. One of the transcripts has an extended exon I with inclusion of most of the first TF intron (955 bp), while the second transcript is formed by the insertion of a 495 bp sequence, referred to as exon IA, derived from an internal sequence of the first intron. The full length TF transcript with alternatively spliced novel exon IA, referred to as alternative exon 1A‐tissue factor (TF‐A), represented ˜1% of the total TF transcripts in normal cells, but constituted 7–10% of the total TF transcript in tumor cells. Quantitative real‐time RT‐PCR analysis indicated that cultured human tumor cells contain 10–25‐fold more copy numbers of TF‐A in comparison to normal, untransformed cells. We propose that high‐level expression of the novel TF‐A transcript, preferentially in tumor cells, may have utility in the diagnosis and staging of a variety of solid tumors. © 2005 Wiley‐Liss, Inc.
Bulky DNA adducts as risk indicator of lung cancer in a Danish case‐cohort study
Authors: Bak Helle , Autrup Herman , Thomsen Birthe Lykke , Tjønneland Anne , Overvad Kim , Vogel Ulla , Raaschou‐Nielsen Ole , Loft Steffen 
Published: October 2005

AbstractLittle is known of the predictive value of the levels of DNA adducts in terms of cancer risk. We examined the association between bulky DNA adducts and risk of lung cancer in a population‐based cohort, comprising of 25,717 men and 27,972 women aged 50–64 years at entry. We included 245 cases (137 men and 108 women) with lung cancer and a comparison group of 255 individuals (137 men and 118 women), matched on sex, age and smoking duration. Bulky adducts in white blood cells collected at enrolment and stored at −150°C were analyzed by 32P‐postlabeling method, using the butanol enrichment procedure. The median level of bulky DNA adducts was 0.196 adduct/108 nucleotides (5–95 percentiles: 0.094–0.595) among current smokers who were later diagnosed with lung cancer and 0.163 adduct/108 nucleotides (5–95 percentiles: 0.091–0.455) among current smokers in the comparison group. The smoking adjusted incidence rate ratios (IRR) for lung cancer in relation to one log unit (natural logarithm) difference in adduct levels were 1.22 (95% CI 0.85–1.74), 1.33 (95% CI 0.89–1.98) and 0.76 (95% CI 0.39–1.47) among all, current and former smokers, respectively. Current smokers with bulky DNA adduct levels above the median had a significant higher lung cancer rate than those with adduct levels below the median (IRR = 1.61; 95% CI 1.04–2.49). The results are compatible with previous studies, suggesting a slightly higher risk of lung cancer with higher levels of adducts among smokers. Our results indicate that bulky DNA adducts may have a weak association with lung cancer risk. © 2005 Wiley‐Liss, Inc.
Heparanase promotes growth, angiogenesis and survival of primary breast tumors
Authors: Cohen Irit , Pappo Orit , Elkin Michael , San Tamara , Bar‐Shavit Rachel , Hazan Rachel , Peretz Tamar , Vlodavsky Israel , Abramovitch Rinat 
Published: October 2005

AbstractDespite great strides toward diagnosis and therapy, breast cancer remains a most threatening disease in its incidence, morbidity and mortality; therefore, additional knowledge regarding the molecular mechanisms contributing to breast cancer progression, as well as new targets for drug discovery are highly needed. Heparanase is the predominant enzyme involved in cleavage of heparan sulfate, the main polysaccharide component of the extracellular matrix. Experimental and clinical data indicate that heparanase plays important roles in cancer metastasis and angiogenesis. In breast carcinoma patients, heparanase expression correlates with the metastatic potential of the tumor. The present study was undertaken to investigate the role of heparanase in local growth and angiogenesis of primary breast tumors. MCF‐7 breast carcinoma cells were stable transfected with the human heparanase (H‐hpa) cDNA, or empty vector (mock), and injected into the mammary pad of nude mice. MRI was applied to monitor progression of tumor growth and angiogenesis. We demonstrate that tumors produced by cells overexpressing heparanase grew faster and were 7‐fold larger than tumors produced by mock transfected cells. This enhanced growth was accompanied by increased tumor vascularization and a higher degree of vessel maturation. Histological examination ascribed the differences in tumor growth to heparanase‐stimulated cell proliferation and survival. In‐vitro experiments reinforced heparanase role as a survival factor under stress conditions. Moreover, H‐hpa tumor cells infiltrate into the adjacent stroma, promoting formation of highly vascularized fibrous bands. Our results emphasize the significance and clarify the involvement of heparanase in primary breast cancer progression by generating a supportive microenvironment that promotes tumor growth, angiogenesis and survival. © 2005 Wiley‐Liss, Inc.
Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations
Authors: Györffy Balazs , Surowiak Paweł , Kiesslich Olaf , Denkert Carsten , Schäfer Reinhold , Dietel Manfred , Lage Hermann 
Published: October 2005

AbstractCancer patients with tumors of similar grading, staging and histogenesis can have markedly different treatment responses to different chemotherapy agents. So far, individual markers have failed to correctly predict resistance against anticancer agents. We tested 30 cancer cell lines for sensitivity to 5‐fluorouracil, cisplatin, cyclophosphamide, doxorubicin, etoposide, methotrexate, mitomycin C, mitoxantrone, paclitaxel, topotecan and vinblastine at drug concentrations that can be systemically achieved in patients. The resistance index was determined to designate the cell lines as sensitive or resistant, and then, the subset of resistant vs. sensitive cell lines for each drug was compared. Gene expression signatures for all cell lines were obtained by interrogating Affymetrix U133A arrays. Prediction Analysis of Microarrays was applied for feature selection. An individual prediction profile for the resistance against each chemotherapy agent was constructed, containing 42–297 genes. The overall accuracy of the predictions in a leave‐one‐out cross validation was 86%. A list of the top 67 multidrug resistance candidate genes that were associated with the resistance against at least 4 anticancer agents was identified. Moreover, the differential expressions of 46 selected genes were also measured by quantitative RT‐PCR using a TaqMan micro fluidic card system. As a single gene can be correlated with resistance against several agents, associations with resistance were detected all together for 76 genes and resistance phenotypes, respectively. This study focuses on the resistance at the in vivo concentrations, making future clinical cancer response prediction feasible. The TaqMan‐validated gene expression patterns provide new gene candidates for multidrug resistance. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat. © 2005 Wiley‐Liss, Inc.
C/EBP homologous protein is necessary for normal osteoblastic function
Authors: Pereira Renata C. , Stadmeyer Lisa , Marciniak Stefan J. , Ron David , Canalis Ernesto 
Published: October 2005

AbstractC/EBP homologous protein (CHOP) suppresses adipogenesis and accelerates osteoblastogenesis in vitro. However, the effects of CHOP in the skeleton in vivo are not known. To investigate the actions of CHOP on bone remodeling, we examined the skeletal phenotype of chop null mice from 1 to 12 months of age. Chop null mice appeared normal and their growth and serum insulin like growth factor (IGF) I and osteocalcin levels were normal. X‐ray analysis of the skeleton revealed no abnormalities and bone mineral density was normal. Static and dynamic histomorphometry revealed that chop null mice had decreased bone formation rates, without changes in osteoblast cell number, indicating an osteoblastic functional defect. The number of osteoblasts and osteoclasts and eroded surface were normal. Northern blot analysis revealed decreased type I collagen and osteocalcin mRNA levels in calvariae of chop null mice. In conclusion, chop null mice exhibit decreased bone formation and impaired osteoblastic function, indicating that CHOP is necessary for the normal expression of the osteoblastic phenotype. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.