bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implication of Mismatch Between Stress and Strain-Rate in Turbulence Subjected to Rapid Straining and Destraining on Dynamic LES Models
Authors: Chen Jun , Katz Joseph , Meneveau Charles 
Published: September 2005

Abstract
Planar straining and destraining of turbulence is an idealized form of turbulence-meanflow interaction that is representative of many complex engineering applications. This paper studies experimentally the response of turbulence subjected to a process involving planar straining, a brief relaxation and destraining. Subsequent analysis quantifies the impact of the applied distortions on model coefficients of various eddy viscosity subgrid-scale models. The data are obtained using planar particle image velocimetry (PIV) in a water tank, in which high Reynolds number turbulence with very low mean velocity is generated by an array of spinning grids. Planar straining and destraining mean flows are produced by pushing and pulling a rectangular piston towards and away from the bottom wall of the tank. The velocity distributions are processed to yield the time evolution of mean subgrid dissipation rate, the Smagorinsky and dynamic model coefficients, as well as the mean subgrid-scale momentum flux during the entire process. It is found that the Smagorinsky coefficient is strongly scale dependent during periods of straining and destraining. The standard dynamic approach overpredicts the dissipation based Smagorinsky coefficient, with the model coefficient at scale Δ in the standard dynamic Smagorinsky model being close to the dissipation based Smagorinsky coefficient at scale 2Δ. The scale-dependent Smagorinsky model, which is designed to compensate for such discrepancies, yields unsatisfactory results due to subtle phase lags between the responses of the subgrid-scale stress and strain-rate tensors to the applied strains. Time lags are also observed for the SGS momentum flux at the larger filter scales considered. The dynamic and scale-dependent dynamic nonlinear mixed models do not show a significant improvement. These potential problems of SGS models suggest that more research is needed to further improve and validate SGS models in highly unsteady flows.
P-DCFOLD OR HOW TO PREDICT ALL KINDS OF PSEUDOKNOTS IN RNA SECONDARY STRUCTURES
Authors: TAHI FARIZA , STEFAN ENGELEN , REGNIER MIREILLE 
Published: September 2005

Pseudoknots play important roles in many RNAs. But for computational reasons, pseudoknots are usually excluded from the definition of RNA secondary structures. Indeed, prediction of pseudoknots increase very highly the complexities in time of the algorithms, knowing that all existing algorithms for RNA secondary structure prediction have complexities at least of O(n3). Some algorithms have been developed for searching pseudoknots, but all of them have very high complexities, and consider generally particular kinds of pseudoknots. We present an algorithm, called P-DCFold based on the comparative approach, for the prediction of RNA secondary structures including all kinds of pseudoknots. The helices are searched recursively using the "Divide and Conquer" approach, searching the helices from the "most significant" to the "less significant". A selected helix subdivide the sequence into two sub-sequences, the internal one and a concatenation of the two externals. This approach is used to search non-interleaved helices and allows to limit the space of searching. To search for pseudoknots, the processing is reiterated. Therefore, each helix of the pseudoknot is selected in a different step. P-DCFold has been applied to several RNA sequences. In less than two seconds, their respective secondary structures, including their pseudoknots, have been recovered very efficiently.
Hypoxia-Inducible Factor 1α Expression as an Intrinsic Marker of Hypoxia
Authors: Hutchison Gillian J. , Valentine Helen R. , Loncaster Juliette A. , Davidson Susan E. , Hunter Robert D. , Roberts Stephen A. , Harris Adrian L. , Stratford Ian J. , Price Patricia M. , West Catharine M. L. 
Published: September 2005

AbstractPurpose: Hypoxia-inducible factor (HIF)-1α expression was studied retrospectively in locally advanced carcinoma of the cervix in relation to other methods for measuring/assessing tumor hypoxia and outcome after radiotherapy.Experimental Design: HIF-1α expression was examined in formalin-fixed tumor biopsies using a semiquantitative scoring system and correlated with measurements of hypoxia obtained using oxygen electrodes, pimonidazole staining, and carbonic anhydrase 9.Results: High HIF-1α expression showed a weak correlation with low pO2 (r = −0.26; P = 0.030; n = 72). Weak significant correlations were found between HIF-1α and pimonidazole staining (r = 0.34; P = 0.040; n = 36) and carbonic anhydrase IX (r = 0.27; P = 0.001; n = 160). There was no relationship with surviving fraction at 2 Gy. The relationship between HIF-1α expression and radiotherapy outcome was examined in 99 patients. HIF-1α expression did not correlate with disease stage, grade, tumor size, and patient age. HIF-1α alone was not a significant prognostic factor for disease-free survival, metastasis-free survival, or local recurrence-free survival. High HIF-1α expression tended to be associated with poor outcome in small tumors but good outcome in large tumors, with statistically significant interactions between HIF-1α and tumor size for survival (P = 0.046) and local control (P = 0.009).Conclusions: In this study, HIF-1α had no prognostic significance in locally advanced carcinoma of the cervix. The possible switch in large tumors for an association between high HIF-1α expression and good outcome might relate to tumor size-related changes in the balance of genes up-regulated by HIF-1α. Whereas angiogenesis-promoting genes might be preferentially up-regulated in small tumors, proapoptotic genes might be induced in large tumors. This hypothesis needs testing in future work.
Molecular Profiling and Classification of Sporadic Renal Cell Carcinoma by Quantitative Methylation Analysis
Authors: Gonzalgo Mark L. , Yegnasubramanian Srinivasan , Yan Gai , Rogers Craig G. , Nicol Theresa L. , Nelson William G. , Pavlovich Christian P. 
Published: September 2005

Abstract
Purpose: Preoperative histologic classification of solid renal masses remains limited with current technology. We determine the utility of molecular profiling based on quantitative methylation analysis for characterization of sporadic renal cell carcinoma.
Experimental Design: Primary renal cell carcinomas representing three different histologic subtypes were obtained from a total of 38 patients who underwent radical nephrectomy for suspected malignant disease. Genomic DNA was isolated from tumors and was subjected to sodium bisulfite modification. The normalized index of methylation (NIM) for each sample was determined by quantitative real-time methylation-specific PCR at 17 different gene promoters. Hierarchical cluster analysis was performed by using an unsupervised neural network with binary tree topology.
Results: The majority of gene promoters that were analyzed in this study demonstrated very low levels of methylation (NIM &lt;1.0). The RASSF1A gene promoter, however, was methylated in 30 of 38 (79%) cases. The frequency of RASSF1A methylation in papillary, clear-cell, and oncocytoma subtypes was 100, 90, and 25%, respectively. The highest levels of RASSF1A methylation were observed in the papillary (mean NIM = 78.9) and clear-cell (mean NIM = 13.4) subtypes. The vast majority of oncocytomas were completely unmethylated, and none demonstrated &gt;1% methylation (mean NIM = 0.11). Hierarchical cluster analysis based on quantitative methylation levels resulted in stratification of sporadic renal cell carcinomas into their discrete histologic subtypes.
Conclusions: Classification of sporadic renal cell carcinomas into histologic subtypes can be accomplished via multigene quantitative methylation profiling. Validation of this approach and selection of appropriate methylation markers may ultimately lead to use of this technology in the preoperative assessment of suspicious renal masses.
Deregulated Cyclin D1 Expression Is Associated with Decreased Efficacy of the Selective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib in Head and Neck Squamous Cell Carcinoma Cell Lines
Authors: Kalish Larry H. , Kwong Rhonda A. , Cole Ian E. , Gallagher Richard M. , Sutherland Robert L. , Musgrove Elizabeth A. 
Published: September 2005

Abstract
Purpose: Despite promising initial results, recent Phase III trials of the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (“Iressa”; AstraZeneca, Wilmington, Delaware) in advanced head and neck squamous cell carcinoma (HNSCC) have been equivocal. Cyclin D1, an EGFR target gene, is frequently overexpressed in HNSCC, has been implicated in its pathogenesis, and is strongly associated with poor prognosis in this disease. Therefore, we examined the relationship between deregulated cyclin D1 expression and sensitivity to gefitinib to determine whether this frequently occurring oncogenic change affected the cellular response to gefitinib.
Experimental Design: A panel of six EGFR-overexpressing HNSCC cell lines was used to correlate CCND1 gene copy number, cyclin D1 expression, and response to gefitinib. The effect of constitutive overexpression of cyclin D1 was assessed by establishing stably transfected clonal SCC-9 cell lines.
Results: Three of six cell lines displayed cyclin D1 amplification and/or overexpression, and these cell lines were resistant to gefitinib. SCC 9 clones overexpressing cyclin D1 continued to proliferate and maintained their S-phase fraction when treated with gefitinib, whereas empty vector control clones and the parental SCC 9 cells were profoundly inhibited and displayed marked reductions in S-phase. The resistance of cyclin D1-overexpressing clones and cyclin D1-amplified cell lines was associated with maintenance of cyclin D1 expression after gefitinib treatment.
Conclusions: These data suggest that deregulated cyclin D1 overexpression may be associated with resistance of HNSCC to EGFR inhibitors. Therefore, the role of cyclin D1 as a marker of therapeutic response and its utility as a prognostic marker in HNSCC warrant additional analysis.
Inhibition of mTOR Activity Restores Tamoxifen Response in Breast Cancer Cells with Aberrant Akt Activity
Authors: deGraffenried Linda A. , Friedrichs William E. , Russell Douglas H. , Donzis Elissa J. , Middleton Amanda K. , Silva Jessica M. , Roth Richard A. , Hidalgo Manuel 
Published: September 2005

Abstract
The Akt kinase is a serine/threonine protein kinase that has been implicated in mediating a variety of biological responses. Studies show that high Akt activity in breast carcinoma is associated with a poor pathophenotype, as well as hormone and chemotherapy resistance. Additionally, high Akt activity is associated with other features of poor prognosis. Thus, a chemotherapeutic agent directed specifically toward tumors with high Akt activity could prove extremely potent in treating those breast tumors with the most aggressive phenotypes. Several studies have demonstrated that rapamycin, which inhibits mammalian target of rapamycin (mTOR), a downstream target of Akt, sensitizes certain resistant cancer cells to chemotherapeutic agents. This study evaluated the efficacy of mTOR inhibition in the treatment of tamoxifen-resistant breast carcinoma characterized by high Akt activity. We found that MCF-7 breast cancer cell lines expressing a constitutively active Akt are able to proliferate under reduced estrogen conditions and are resistant to the growth inhibitory effects of tamoxifen, both in vitro as well as in vivo in xenograft models. Cotreatment with the mTOR inhibitor rapamycin in vitro, or the ester of rapamycin, CCI-779 (Wyeth) in vivo, inhibited mTOR activity and restored sensitivity to tamoxifen, suggesting that Akt-induced tamoxifen resistance is mediated in part by signaling through the mTOR pathway. Although the mechanism underlying the synergism remains to be understood, the results were associated with rapamycin’s ability to block transcriptional activity mediated by estrogen receptor α, as assessed by reporter gene assays with estrogen-responsive element luciferase. These data corroborate prior findings indicating that Akt activation induces resistance to tamoxifen in breast cancer cells. Importantly, these data indicate a novel mechanism for tamoxifen resistance and suggest that blockage of the phosphatidylinositol 3′-kinase/Akt signaling pathway by mTOR inhibition effectively restores the susceptibility of these cells to tamoxifen. These data may have implication for future clinical studies of mTOR inhibition in breast carcinoma.
Ring Finger Protein 43 as a New Target for Cancer Immunotherapy
Authors: Uchida Naotaka , Tsunoda Takuya , Wada Satoshi , Furukawa Yoichi , Nakamura Yusuke , Tahara Hideaki 
Published: September 2005

Abstract
We have performed genome-wide exploration by using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes (CTLs) specific to tumor cells. In our preceding study, we identified multiple new genes by using gene expression profiling with a genome-wide cDNA microarray containing 23,040 genes. Among them, we selected RNF43 (ring finger protein 43) as a promising candidate for a TAA expressed by colon cancer cells. In this study, we examined whether the RNF43 protein contains antigenic epitope peptides restricted to HLA-A*0201 or HLA-A*2402. The CTL clones were successfully induced with stimulation by using the peptides binding to HLA-A*0201 (ALWPWLLMA and ALWPWLLMAT) and HLA-A*2402 (NSQPVWLCL), and these CTL clones showed the cytotoxic activity specific to not only the peptide-pulsed targets but also the tumor cells expressing RNF43 and respective HLAs. Lytic activities mediated by two HLA-A2-restricted epitopes were marginal, whereas tumor lysis mediated by the HLA-A24 epitope was clearly better. These findings might be caused by the poor natural presentation of RNF43-11(IX) and RNF43-11(X) by tumors or poor T-cell receptor avidity for these specific epitopes. These results strongly suggest that RNF43 is a new TAA of colon cancer. Furthermore, these results also suggest that our strategy might be a promising one to efficiently discover clinically useful TAAs.
Delineation of Brain Tumor Extent with [11C]l-Methionine Positron Emission Tomography
Authors: Kracht Lutz W. , Miletic Hrvoje , Busch Susanne , Jacobs Andreas H. , Voges Jurgen , Hoevels Moritz , Klein Johannes C. , Herholz Karl , Heiss Wolf-D. 
Published: September 2005

Abstract
Purpose: Methyl-[11C]l-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts.
Experimental Design: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes.
Results: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P &lt; 0.003).
Conclusions: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.
Antiproliferative Effects of Interferon-αCon1 on Ovarian Clear Cell Adenocarcinoma
In vitro
and
In vivo
Authors: Takemoto Yumi , Yano Hirohisa , Momosaki Seiya , Ogasawara Sachiko , Nishida Naoyo , Kojiro Sakiko , Kamura Toshiharu , Kojiro Masamichi 
Published: September 2005

Abstract
Purpose: We examined the antiproliferative effect of IFN-αCon1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo.
Experimental Design: (a) The effects of IFN-αCon1 on growth, morphology, cell cycle, and type I IFN-α receptor (IFNAR-2) expression were examined on two ovarian clear cell adenocarcinoma cell lines (KOC-5C and KOC-7C) in vitro. (b) KOC-5C or KOC-7C cells were transplanted into nude mice, and changes in tumor volume, tumor weight, apoptosis, necrosis, and microvessel density were investigated. The expression of angiogenesis factors was examined in the serum and the developed tumors.
Results: Both cell lines expressed IFNAR-2 mRNA, but its protein was detected only in KOC-7C. In KOC-7C cells, antiproliferative effects were observed in a time- and dose-dependent manner and cell division was blocked at the S phase. The KOC-7C tumors showed decreases in tumor volume and weight; a decreasing tendency in basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and interleukin (IL)-8 protein expression in the tumor; a significant decrease in bFGF and IL-8 protein expression in the serum, and of microvessel density; and significant increase in apoptosis and necrosis in the tumor. In the KOC-5C tumors, these in vitro and in vivo changes were not apparent, and the antiproliferative effects of IFN-αCon1 were not obvious.
Conclusions: IFN-αCon1 suppresses tumor proliferation by inducing apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis. Our findings show that the clinical efficacy of IFN-αCon1 can be predicted by examining IFNAR-2 expression on tumor cells, and the efficacy of IFN-αCon1 treatment can be evaluated by measuring serum bFGF and IL-8 levels.
HMGA1 Protein Overexpression in Human Breast Carcinomas
Authors: Chiappetta Gennaro , Botti Gerardo , Monaco Mario , Pasquinelli Rosa , Pentimalli Francesca , Di Bonito Maurizio , D’Aiuto Giuseppe , Fedele Monica , Iuliano Rodolfo , Palmieri Emiliano A. , Pierantoni Giovanna Maria , Giancotti Vincenzo , Fusco Alfredo 
Published: September 2005

Abstract
We measured, by immunohistochemistry, HMGA1 protein expression in 212 breast tissue specimens: 6 normal samples, 28 hyperplastic lesions (13 with cellular atypia), 11 fibroadenomas, 10 in situ ductal carcinomas, 144 ductal carcinomas, and 13 lobular carcinomas. HMGA1 was not expressed in normal breast tissue; HMGA1 staining was intense in 40% of hyperplastic lesions with cellular atypia and in 60% of ductal carcinomas and weak in fibroadenomas and in hyperplastic lesions without cellular atypia. Because HMGA1 expression was similar among ductal breast carcinomas with different histologic grading, we evaluated the association between HMGA1 expression and that of other markers of breast carcinoma invasion (estrogen and progesterone receptors, Ki-67 antigen, and ErbB2) in 21 cases of grade 3 breast ductal carcinomas and 7 cases of breast lobular carcinomas. We found that HMGA1 expression tended to be associated only with c-erbB-2 expression (Spearman rho: 0.36; P = 0.065). Taken together, these results suggest that HMGA1 expression might be a novel indicator for the diagnosis and prognosis of human breast cancer.
A Pilot Surrogate End Point Biomarker Trial of Perillyl Alcohol in Breast Neoplasia
Authors: Stearns Vered , Coop Andrew , Singh Baljit , Gallagher Ann , Yamauchi Hideko , Lieberman Ronald , Pennanen Marie , Trock Bruce , Hayes Daniel F. , Ellis Matthew J. 
Published: September 2005

Abstract
Purpose: Efficient strategies to screen promising agents in early phase development are essential for rapid progress in breast cancer chemoprevention. We report our experience with the natural compound perillyl alcohol (POH) administered in a short-term surrogate end point biomarker (SEB) protocol, using the “window” between diagnostic and definitive surgery.
Experimental Design: Eligible patients included those with a diagnosis of atypical ductal hyperplasia, ductal carcinoma in situ, lobular carcinoma in situ, or invasive carcinoma (&lt;3 cm in size) that required further surgery. Thirty-seven of 267 women screened were enrolled in the study (14%). Five women received single-dose POH (1.5 g/m2) 2 days before surgery, 16 received escalating doses of POH (1.2 g/m2 to 4.8 g/m2/day) for 2 days before surgery, and 16 served as untreated controls. Exploratory SEB analysis [estrogen receptor, progesterone receptor, proliferation, apoptosis, M6P/insulin-like growth factor (IGF)-2R, IGF1, IGF2 and transforming growth factor β] was conducted before and after POH.
Results: Only a small portion of the population screened entered the study. Reasons for nonparticipation included protocol ineligibility, conflict of timing of surgery, miscellaneous logistical reasons, or patient’s choice. POH administration was well tolerated and did not interfere with surgical management. The power to observe changes in candidate SEB was diminished by a 44% incidence of cases in which the index lesion was not present in the definitive surgical specimen.
Conclusions: Preoperative POH exposure was safe and suitable for a more definitive phase II SEB study. Further investigations must overcome logistical obstacles to accrual, and they must focus on approaches to maximize tissue collection and to incorporate genomic analysis of target lesions.
A Phase II Trial of Gefitinib (Iressa, ZD1839) in Stage IV and Recurrent Renal Cell Carcinoma
Authors: Dawson Nancy A. , Guo Chuanfo , Zak Richard , Dorsey Brenda , Smoot Jeanne , Wong Jade , Hussain Arif 
Published: September 2005

Abstract
Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in 75 to 90% of renal cell carcinomas and may play a role in tumor initiation and progression. Gefitinib (Iressa, ZD1839) is a potent, selective EGFR-tyrosine kinase inhibitor. This trial was undertaken to assess the efficacy and toxicity of gefitinib in advanced renal cell carcinoma.
Experimental Design: Oral gefitinib, 500 mg once daily, was given continuously. A single-dose reduction to 250 mg daily was allowed for toxicity. The primary end point was response rate (defined as complete remission + partial remission + stable disease). Secondary end points were progression-free survival, overall survival, toxicity, and correlation of response with EGFR status.
Results: Twenty-one patients were enrolled on this study, and all are evaluable for response and toxicity. Patient characteristics were median age 61 (range, 35–78 years); 17 males, 4 females; median performance status 0 (range 0–2); median number of prior systemic therapies 1 (range, 0–3). The median and mean number of cycles of therapy received was 3 and 4.7 (range, 1–14+). The best response was stable disease in eight patients (38%). Median progression-free survival was 2.7 months. Median overall survival was 8.3 months. The difference in overall survival was significantly different between patients with progressive disease versus stable disease (6.1 months versus 16+ months; Log-Rank test P value &lt; 0.0001). Three patients required a dose reduction, all for grade 3 diarrhea. There was no apparent correlation between EGFR status and stability of disease or progression of disease.
Conclusions: Gefitinib is without significant conventional activity in renal cell carcinoma. The relation of “stable disease” to treatment or to disease-related prognostic heterogeneity remains to be defined.