bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective antibody‐mediated targeting of class I MHC to EGFR‐expressing tumor cells induces potent antitumor CTL activity in vitro and in vivo
Authors: Novak Hila , Noy Roy , Oved Kfir , Segal Dina , Wels Winfried S. , Reiter Yoram 
Published: October 2006

AbstractEpidermal growth factor receptor (EGFR) is highly overexpressed in many tumor types. We present a new fusion molecule that can target solid tumors that express EGFR. The fusion molecule combines the advantage(s) of the well‐established tumor targeting capabilities of high affinity recombinant fragments of antibodies with the known efficient, specific and potent killing ability of CD8 T lymphocytes directed against highly antigenic MHC/peptide complexes. A recombinant chimeric molecule was created by the genetic fusion of the scFv antibody fragment derived from the anti‐EGFR monoclonal antibody C225, to monomeric single‐chain HLA‐A2 complexes containing immunodominant tumor or viral‐specific peptides. The fusion protein can induce very efficiently CTL‐dependent lysis of EGFR‐expressing tumor cells regardless of the expression of self peptide‐MHC complexes. Moreover, the molecule exhibited very potent antitumor activity in vivo in nude mice bearing preestablished human tumor xenografts. These in vitro and in vivo results indicate that recombinant scFv‐MHC‐peptide fusion molecules might represent a novel and powerful approach to immunotherapy of solid tumors, bridging antibody and T lymphocyte attack on cancer cells. © 2006 Wiley‐Liss, Inc.
Risk of breast cancer in female survivors of childhood Hodgkin's disease in Britain: A population‐based study
Authors: Taylor Aliki J. , Winter David L. , Stiller Charles A. , Murphy Mike , Hawkins Mike M. 
Published: October 2006

AbstractThere is now widespread evidence that female survivors of Hodgkin's disease who have been treated with supradiaphragmatic radiotherapy are at an increased risk of breast cancer. Mantle irradiation, which includes irradiation of the mediastinum, conveys a particularly high risk. Previously published studies have found a wide variation in risk. To provide British estimates of risk to inform surveillance programmes, we carried out the first British population‐based cohort study of breast cancer in female survivors of childhood Hodgkin's disease. From the underlying cohort of the British Childhood Cancer Survivor Study, a cohort of 18,123 British 5‐year survivors of childhood cancer diagnosed between 1940 and 1991, there were in total 383 female 5‐year survivors of childhood Hodgkin's disease. Sixteen of these 383 survivors went on to develop invasive breast cancer subsequent to 5‐year survival (standardised incidence ratio, 11.5; 95% confidence interval (95% CI), 6.6–18.6) and all of these 16 survivors had been treated with supradiaphragmatic irradiation as treatment for childhood Hodgkin's disease. The cumulative risk of breast cancer by 25 years of follow up was 9.9% (95% CI, 3.3–16.6) for all patients and 12.2% (95% CI, 4.3–20.1) for those treated with supradiaphragmatic radiotherapy. The cumulative risk of breast cancer in female survivors of childhood Hodgkin's disease in Britain is at the lower end of previous estimates. We hope that our data may provide a basis for future surveillance and for counselling survivors as to their likely risk of breast cancer. © 2006 Wiley‐Liss, Inc.
Nonrandom distribution of oncogene amplifications in bilateral breast carcinomas: Possible role of host factors and survival bias
Authors: Suspitsin Evgeny N. , Sokolenko Anna P. , Togo Alexandr V. , Lazareva Yulia R. , Turkevich Elena A. , Matsko Dmitry E. , Henrich Kai‐Oliver , Borresen‐Dale Anne‐Lise , Schwab Manfred , Cornelisse Cees J. , Imyanitov Evgeny N. 
Published: October 2006

AbstractAmplification of HER2, C‐MYC and CCND1 oncogenes is a hallmark of breast cancer (BC); however, its involvement in the bilateral form of this disease has not been investigated yet. In this study, 50 bilateral BC (biBC) pairs (100 tumors) and 72 control unilateral BC were examined using real‐time PCR analysis of microdissected archival tissues. In biBC, the frequency of >3‐fold oncogene amplification was 6/100 (6%) for HER2, 6/100 (6%) for C‐MYC and 7/100 (7%) for CCND1. Altogether, 18/100 (18%) biBC tumors had increased gene dosage of at least one oncogene. Tumors forming synchronous biBC pairs had amplification in 11/46 cases (24%). In 3 of 8 patients with amplification‐positive carcinomas, the amplification was detected in both neoplasms: 2 biBC had concordant activation of the same oncogene (HER2 and CCND1, respectively), and in the remaining case distinct oncogenes were affected (HER2 and C‐MYC). In contrast, amplifications in metachronous biBC were strongly discordant: none of 27 first carcinomas carried this abnormality, while the frequency of amplification in second tumors (7/27; 26%) was similar to the one observed in unilateral BC (20/72; 28%). The trend toward concordance of oncogene amplification status in synchronous but not in metachronous biBC pairs can be explained by the nearly identical natural history of the disease in simultaneously arising tumors. The skewed pattern of amplifications in metachronous biBC might be attributed to their association with adverse BC prognosis; it appears that only patients with amplification‐negative first BC have sufficient chances to survive until the development of the contralateral carcinoma. © 2006 Wiley‐Liss, Inc.
Detection of novel quantitative trait loci for cutaneous melanoma by genome‐wide scan in the MeLiM swine model
Authors: Zhi‐Qiang Du , Silvia Vincent‐Naulleau , Hélène Gilbert , Florence Vignoles , Françoise Créchet , Takeshi Shimogiri , Hiroshi Yasue , Jean‐Jacques Leplat , Stephan Bouet , Joseph Gruand , Vratislav Horak , Denis Milan , Roy Pascale Le , Claudine Geffrotin 
Published: October 2006

AbstractHuman cutaneous melanoma is a complex trait inherited in about 10% of cases. Although 2 high‐risk genes, CDKN2A and CDK4, and 1 low risk gene, MC1R, have been identified, susceptibility genes remain to be discovered. Here, we attempted to determine new genomic regions linked to melanoma using the pig MeLiM strain, which develops hereditary cutaneous melanomas. We applied quantitative trait loci (QTL) mapping method to a significant genome‐wide scan performed on 331 backcross pigs derived from this strain. QTLs were detected at chromosome‐wide level for a melanoma synthetic trait corresponding to the development of melanoma. The peak positions on Sus scrofa chromosomes (SSC) were at 49.4 and 88.0 cM (SSC1), 56.0 cM (SSC13), 86.5 cM (SSC15) and 39.8 cM (SSC17), and, on SSC2, at 16.9 cM, in families derived from F1 males only (p < 0.05, except for SSC13, p < 0.01). Analysis of 7 precise specific traits revealed highly significant QTLs on SSC10 (ulceration), on SSC12 (presence of melanoma at birth), on SSC13 (lesion type), and on SSC16 and SSC17 (number of aggressive melanomas) at the respective positions 42.0, 95.6, 81.0, 45.3 and 44.8 cM (p < 0.001 and p < 0.05 respectively at the chromosome‐ and genome‐wide levels). We also showed that MeLiM MC1R*2 allele, which determines black coat colour in pigs, predisposes significantly to melanoma. Interactions were observed between MC1R and markers located on SSC1 (p < 0.05). Taken together, these results indicate that MeLiM swine is a model for human multigenic diseases. Comparative mapping revealed human regions of interest to search for new melanoma susceptibility candidates. © 2006 Wiley‐Liss, Inc.
Progression of tumors arising from large ACF is associated with the MUC5AC expression during rat colon MNNG carcinogenis
Authors: Maurin Nicole , Forgue‐Lafitte Marie‐Elisabeth , Levy Pierre , Zimber Amazia , Bara Jacques 
Published: October 2006

AbstractAberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomas, precursors of colon cancer. The gastric M1/MUC5AC mucin has also been described as an early marker of colon carcinogenesis in the human and in the rat. To study changes in mucin expression associated with the genesis of tumors, Wistar rats were treated by intrarectal instillations of MNNG, twice a week for 2 weeks, and were sacrificed 10 (n = 20), 14 (n = 20), 22 (n = 20), 30 (n = 10) and 66 (n = 16) weeks after the beginning of the treatment. In the treated rats, the MUC5AC mucin was mainly expressed in ACF compared with the histologically normal mucosae, which showed few isolated MUC5AC‐positive normal crypts. During carcinogenesis, the percentage of large ACF [≥≥10 aberrant crypts] increased and the number of MUC5AC‐positive (NCs) decreased. At Week 30, small tumors were observed arising from large ACF, both types of lesions expressing MUC5AC. At Week 66, large tumors showed remnants of MUC5AC‐positive ACF in their adjacent mucosae. This observation suggests that the expression of MUC5AC is associated with the ACF/adenoma sequence and supports the notion of large ACF as precursors of adenomas/adenocarcinomas. Moreover, the expression of MUC5AC in the transitional mucosa adjacent to both rat and human colon tumors suggests that some human tumors could arise from large ACF, and reinforces the concept of the premalignant potential of these lesions. © 2006 Wiley‐Liss, Inc.
The interaction of adenovirus E1A with p300 family members modulates cellular gene expression to reduce tumorigenicity
Authors: Miura Tanya A. , Cook James L. , Potter Terence A. , Ryan Sharon , Routes John M. 
Published: October 2006

AbstractThe use of adenovirus serotype 2 or 5 (Ad2/5) E1A as therapy for human malignancy requires an understanding of the mechanisms involved in E1A‐induced tumor suppression. The prevailing use of E1A in the treatment of human malignancy stresses the non‐immunologically mediated, anti‐tumorigenic activities of E1A. However, the capacity of E1A to elicit a NK‐cell and T‐cell anti‐tumor immune response and to sensitize tumor cells to lysis by immune effector molecules utilized by NK cells and T cells is also an important component of the anti‐tumorigenic activity of E1A. This immune‐mediated anti‐tumorigenic activity of E1A is not shared by functionally similar viral oncoproteins such as the human papillomavirus type 16 (HPV16) E7 oncoprotein and is dependent on the capacity of E1A to interact with transcriptional coadapter, p300. To further define the molecular mechanisms whereby E1A reduces tumorigenicity, we compared total cellular gene expression in H4 cells, a human fibrosarcoma cell line, to gene expression in H4 cells stably expressing E1A, E7, or mutant forms of E1A that do not bind p300. The expression of E1A, but not E7, in H4 cells modulated the expression of cellular genes that may promote apoptosis, enhance immunogenicity and reduce tumor cell metastasis. The difference in the ability of E1A and E7 to modulate the expression of cellular genes that may influence tumorigenicity was largely attributable to distinct interactions of E1A and E7 with p300. Results of this study will be useful in designing novel strategies to augment the anti‐tumorigenic activities of E1A. J. Cell. Biochem. 100: 929–940, 2007. © 2006 Wiley‐Liss, Inc.
Radiation‐induced bystander effect: Activation of signaling molecules in K562 erythroleukemia cells
Authors: Mitra Anirban Kumar , Krishna Malini 
Published: October 2006

AbstractGap junction independent signaling mechanism was investigated using K562 human erythroleukemia cells. They were exposed to 2, 5, or 10 Gy of 60Co γ irradiation, the medium isolated 20 min post‐irradiation and added to fresh cells. Evidence of radiation‐induced bystander effect was observed wherein there was activation of p21, nuclear factor‐κB (NF‐κB), Bax, Bcl‐2 and cleavage of poly(ADP‐ribose) polymerase in bystander cells. The study implicates the involvement of signaling molecules released into the medium and factors like stable free radicals that are generated in the surrounding medium. The response elicited appears to be primarily via NF‐κB and p21 activation. J. Cell. Biochem. 100: 991–997, 2007. © 2006 Wiley‐Liss, Inc.
The kinetics of p53‐binding and histone acetylation at target promoters do not strictly correlate with gene expression after UV damage
Authors: Magrini Roberta , Russo Debora , Fronza Gilberto , Inga Alberto , Menichini Paola 
Published: October 2006

AbstractWe have addressed the correlation between sequence‐specific DNA binding by the tumor suppressor p53 and transactivation of various target genes, in the context of UV irradiation responses. In A549 cells (p53WT), p53 occupancy at the p21, mdm2, and puma promoters increased significantly after UV irradiation. In contrast, p21 mRNA levels did not change, mdm2 mRNA decreased and both p21 and mdm2 proteins were downregulated shortly after UV. At later times, higher p53 occupancy correlated with enhanced expression of these two genes both at mRNA and protein levels. In the p53 mutant cell lines LX1 (R273H) and SKMes1 (R280K), no significant p53‐binding was detected at the gene targets analyzed. Accordingly, p21 and mdm2 proteins were not upregulated after UV irradiation. The kinetics of histone acetylation did not strictly correlate with gene expression. In fact, high levels of acetylated H3 (AcH3) and, particularly, acetylated H4 (AcH4) histones were found shortly after UV irradiation on p21 and mdm2 promoters. At the later time point, when transactivation was detected, acetylation levels decreased significantly although remaining higher than basal levels. Our results indicate that p53 transcription‐dependent and ‐independent responses are activated with different kinetics after UV, possibly relating to the repair of UV‐induced DNA damage. Based on the histone acetylation pattern we hypothesize that the DNA repair function of p53, associated to global genome repair and foci of DNA damage, may be relevant for all p53‐binding sites, including those where occupancy by p53 is also associated to transcriptional modulation. J. Cell. Biochem. 100: 1276–1287, 2007. © 2006 Wiley‐Liss, Inc.
Observation and characterisation of rainfall over Hawaii and surrounding region from the Tropical Rainfall Measuring Mission
Authors: Kidd Chris , McGregor Glenn 
Published: October 2006

AbstractSatellite observations of clouds and precipitation have a history stretching back over 40 years. The observations of clouds initially led to the inference of precipitation from cloud top features and subsequently more direct methods derived from passive microwave observations. More recently, the Tropical Rainfall Measuring Mission (TRMM) has provided unprecedented information from the first active microwave instrument specifically designed to measure rainfall, the precipitation radar (PR). This paper utilises data from the TRMM PR for the period December 1997 to November 2005 to investigate rainfall over Hawaii and the surrounding ocean. The PR instrument not only provides spatial information on rainfall, but also vertical profiles of precipitation. Data from the PR instrument is used to map rainfall at a spatial resolution of 5 km and, utilising the information from the vertical profiles, map the distribution of trade‐wind and non‐trade‐wind precipitation. This paper provides quantitative estimates of rainfall over Hawaii and the surrounding ocean that generally match those of surface observations and models. It is found that the islands exert a significant influence on the distribution of the amount and occurrence of precipitation over this region. Copyright © 2006 Royal Meteorological Society
Predictions of future climate change in the caribbean region using global general circulation models
Authors: Angeles Moises E. , Gonzalez Jorge E. , Erickson David J. , Hernández José L. 
Published: October 2006

AbstractSince the 1800s the global average CO2 mixing ratio has increased and has been related to increases in surface air temperature (0.6 ± 0.2 °C) and variations in precipitation patterns among other weather and climatic variables. The Small Island Developing States (SIDS), according to the 2001 report of the Intergovernmental Panel on Climate Change (IPCC), are likely to be among the most seriously impacted regions on Earth by global climate changes. In this work, three climate change scenarios are investigated using the Parallel Climate Model (PCM) to study the impact of the global anthropogenic CO2 concentration increases on the Caribbean climate. A climatological analysis of the Caribbean seasonal climate variation was conducted employing the National Center for Environmental Prediction (NCEP) reanalysis data, the Xie–Arkin precipitation and the Reynolds–Smith Sea Surface Temperature (SST) observed data. The PCM is first evaluated to determine its ability to predict the present time Caribbean climatology. The PCM tends to under predict the SSTs, which along with the cold advection controls the rainfall variability. This seems to be a main source of bias considering the low model performance to predict rainfall activity over the Central and southern Caribbean. Future predictions indicate that feedback processes involving evolution of SST, cloud formation, and solar radiative interactions affect the rainfall annual variability simulated by PCM from 1996 to 2098. At the same time two large‐scale indices, the Southern Oscillation Index (SOI) and the North Atlantic Oscillation (NAO) are strongly related with this rainfall annual variability. A future climatology from 2041 to 2058 is selected to observe the future Caribbean condition simulated by the PCM. It shows, during this climatology range, a future warming of approximately 1 °C (SSTs) along with an increase in the rain production during the Caribbean wet seasons (early and late rainfall seasons). Although the vertical wind shear is strengthened, it typically remains lower than 8 m/s, which along with SST > 26.5 °C provides favorable conditions for possible future increases in tropical storm frequency. Copyright © 2006 Royal Meteorological Society
Sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma
Authors: Kwak Cheol , Park Yong Hyun , Jeong Chang Wook , Jeong Hyeon , Lee Sang Eun , Moon Kyung Chul , Ku Ja Hyeon 
Published: October 2006

AbstractBackgroundThe objective of the current study was to determine the significance of sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma (RCC).MethodsPatients with metastatic RCC were included in this study and were categorized according to sarcomatoid differentiation.ResultsPatients with sarcomatoid differentiation had more aggressive tumor characteristics than those without sarcomatoid differentiation. After immunotherapy, the median progression‐free survival was 9.0 months (95% confidence interval [CI] 1.4–52.7) for patient without sarcomatoid differentiation and 3.2 months (95% CI 0.4–42.9) for patients with sarcomatoid differentiation, respectively (P = 0.0001). The median overall survival was 22.2 months (95% CI 3.2–75.4) and 10.0 months (95% CI 0.7–60.1) in both groups. When comparing patients with sarcomatoid differentiation, there was no significant difference of overall survival in the immunotherapy group and the no immunotherapy group. Multivariate Cox proportional hazards model analysis showed that T stage (Hazard ratio [HR] 1.71; 95% CI 1.07–2.74; P = 0.024), sarcomatoid differentiation (HR 2.18; 95% CI 1.30–3.66; P = 0.003), and the number of metastasis sites (HR 1.81; 95% CI 1.14–2.88; P = 0.012) were independent predictors of progression‐free survival. Sarcomatoid differentiation and the number of metastasis sites were independent prognostic predictors of overall survival. The estimated relative risks of sarcomatoid differentiation and the number of metastasis sites were 2.83 (95% CI 1.49–5.40; P = 0.002) and 2.31 (95% CI 1.29–4.16; P = 0.005), respectively.ConclusionsOur findings suggest that sarcomatoid differentiation is an important prognostic factor for immunotherapy in metastatic RCC. J. Surg. Oncol. © 2006 Wiley‐Liss, Inc.
Tissue factor expression is a clinical indicator of lymphatic metastasis and poor prognosis in gastric cancer with intestinal phenotype
Authors: Yamashita Hiroharu , Kitayama Joji , Ishikawa Makoto , Nagawa Hirokazu 
Published: October 2006

AbstractBackground and ObjectivesTissue factor (TF), which normally safeguards vascular integrity by inducing hemostasis upon injury, has received widespread attention in the pathogenesis of cancer progression and metastasis. Aberrantly expressed TF in cancer cells has been reported to be associated with advanced stages of malignancy in various cancers.MethodsThe expression of TF and microvessel density (MVD) were immunohistochemically evaluated in 207 gastric cancers, and their relationship with clinicopathological features was examined.ResultsTF was preferentially expressed (41.8%) in intestinal‐type cancer at a significantly higher rate than that in diffuse‐type cancer (12.1%, P < 0.0001). The expression of TF was associated with advanced stage of disease and showed a positive correlation with a higher rate of lymphatic and venous invasion and lymphatic metastasis in intestinal‐type, but not in diffuse‐type carcinoma. Moreover, TF expression was associated with high MVD in the tumor and a worse outcome only in intestinal‐type carcinoma.ConclusionsTF may be critically involved in tumor progression in intestinal‐type, but not in diffuse‐type, gastric carcinoma. The difference in clinical features between these two histological types might be partially dependent on TF expression profile. J. Surg. Oncol. © 2006 Wiley‐Liss, Inc.
Preparation and application of poly(dimethylsiloxane)/β‐cyclodextrin solid‐phase microextraction fibers
Authors: Fu Yue‐li , Hu Yu‐ling , Zheng Yan‐jie , Li Gong‐Ke 
Published: October 2006

AbstractA novel poly(dimethylsiloxane)/β‐cyclodextrin (PDMS/β‐CD) coating was prepared for solid‐phase microextraction (SPME). The PDMS/β‐CD coating proved to have a porous structure, providing high surface areas and allowing for high extraction efficiency. The coating had a high thermal stability (340°C) and a long lifetime due to its chemical binding to the fiber surface. Polar phenols and amines were used to evaluate the character of the coating fiber by headspace (HS) extraction and thermal desorption, followed by GC–FID analysis. Parameters that affected the extraction process were investigated; these include extraction time and temperature, desorption time, pH, and ionic strength of the solution. For phenols, the range of linearity of the method was 4–500 μg/L and the LOD was 1.3–2.1 μg/L. For amines, the range of linearity was 1–1000 μg/L and the LOD was 1.2–2.8 μg/L. The presence of β‐CD not only increases the thermal stability of the fiber coating, but also enhances its selectivity. Compared with commercially available SPME fibers, the new phases show better selectivity and sensitivity towards polar compounds.