bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiosensitization and Modulation of p44/42 Mitogen-Activated Protein Kinase by 2-Methoxyestradiol in Prostate Cancer Models
Authors: Casarez Eli V. , Dunlap-Brown Marya E. , Conaway Mark R. , Amorino George P. 
Published: September 2007

Abstract
2-Methoxyestradiol (2ME2) is an endogenous estradiol metabolite that inhibits microtubule polymerization, tumor growth, and angiogenesis. Because prostate cancer is often treated with radiotherapy, and 2ME2 has shown efficacy as a single agent against human prostate carcinoma, we evaluated 2ME2 as a potential radiosensitizer in prostate cancer models. A dose-dependent decrease in mitogen-activated protein kinase phosphorylation was observed in human PC3 prostate cancer cells treated with 2ME2 for 18 h. This decrease correlated with in vitro radiosensitization measured by clonogenic assays, and these effects were blocked by the expression of constitutively active MEK. Male nude mice with subcutaneous PC3 xenografts in the hind leg were treated with 2ME2 (75 mg/kg) p.o. for 5 days, and 2 Gy radiation fractions were delivered each day at 4 h after drug treatment. A statistically significant super-additive effect between radiation and 2ME2 was observed in this subcutaneous model, using analysis of within-animal slopes. A PC-3M orthotopic model was also used, with bioluminescence imaging as an end point. PC-3M cells stably expressing the luciferase gene were surgically implanted into the prostates of male nude mice. Mice were given oral doses of 2ME2 (75 mg/kg), with radiation fractions (3 Gy) delivered 4 h later. Mice were then imaged weekly for 4 to 5 weeks with a Xenogen system. A significant super-additive effect was also observed in the orthotopic model. These data show that 2ME2 is an effective radiosensitizing agent against human prostate cancer xenografts, and that the mechanism may involve a decrease in mitogen-activated protein kinase phosphorylation by 2ME2. [Cancer Res 2007;67(17):8316–24]
Mistaken Identity of Widely Used Esophageal Adenocarcinoma Cell Line TE-7
Authors: Boonstra Jurjen J. , van der Velden Albertina W. , Beerens Erwin C.W. , van Marion Ronald , Morita-Fujimura Yuiko , Matsui Yasuhisa , Nishihira Tetsuro , Tselepis Chris , Hainaut Pierre , Lowe Anson W. , Beverloo Berna H. , van Dekken Herman , Tilanus Hugo W. , Dinjens Winand N.M. 
Published: September 2007

Abstract
Cancer of the esophagus is the seventh leading cause of cancer death worldwide. Esophageal carcinoma cell lines are useful models to study the biological and genetic alterations in these tumors. An important prerequisite of cell line research is the authenticity of the used cell lines because the mistaken identity of a cell line may lead to invalid conclusions. Estimates indicate that up to 36% of the cell lines are of a different origin or species than supposed. The TE series, established in late 1970s and early 1980s by Nishihira et al. in Japan, is one of the first esophageal cancer cell line series that was used throughout the world. Fourteen TE cell lines were derived from human esophageal squamous cell carcinomas and one, TE-7, was derived from a primary esophageal adenocarcinoma. In numerous studies, this TE-7 cell line was used as a model for esophageal adenocarcinoma because it is one of the few esophageal adenocarcinoma cell lines existing. We investigated the authenticity of the esophageal adenocarcinoma cell line TE-7 by xenografting, short tandem repeat profiling, mutation analyses, and array-comparative genomic hybridization and showed that cell line TE-7 shared the same genotype as the esophageal squamous cell carcinoma cell lines TE-2, TE-3, TE-12, and TE-13. In addition, for more than a decade, independent TE-7 cultures from Japan, United States, United Kingdom, France, and the Netherlands had the same genotype. Examination of the TE-7 cell line xenograft revealed the histology of a squamous cell carcinoma. We conclude that the TE-7 cell line, used in several laboratories throughout the world, is not an adenocarcinoma, but a squamous cell carcinoma cell line. Furthermore, the cell lines TE-2, TE-3, TE-7, TE-12, and TE-13 should be regarded as one single squamous cell carcinoma cell line. [Cancer Res 2007;67(17):7996–8001]
Requirement for Rac1 in a K-ras–Induced Lung Cancer in the Mouse
Authors: Kissil Joseph L. , Walmsley Marita J. , Hanlon Linda , Haigis Kevin M. , Bender Kim Carla F. , Sweet-Cordero Alejandro , Eckman Matthew S. , Tuveson David A. , Capobianco Anthony J. , Tybulewicz Victor L.J. , Jacks Tyler 
Published: September 2007

Abstract
Given the prevalence of Ras mutations in human cancer, it is critical to understand the effector pathways downstream of oncogenic Ras leading to transformation. To directly assess the requirement for Rac1 in K-ras–induced tumorigenesis, we employed a model of lung cancer in which an oncogenic allele of K-ras could be activated by Cre-mediated recombination in the presence or absence of conditional deletion of Rac1. We show that Rac1 function is required for tumorigenesis in this model. Furthermore, although Rac1 deletion alone was compatible with cell viability and proliferation, when combined with K-ras activation in primary epithelial cells, loss of Rac1 caused a profound reduction in proliferation. These data show a specific requirement for Rac1 function in cells expressing oncogenic K-ras. [Cancer Res 2007;67(17):8089–94]
Acknowledgement of Priority
Authors: Cherchye Laurens , Vermeulen Frederic 
Published: September 2007

Robust Rankings of Multidimensional Performances: An Application to Tour de France Racing Cyclists Dr. Knut M. Wittkowski (The Rockefeller University) pointed out that his u-score given in Equation 3 of Wittkowski (2003) and Equation 3 in Wittkowski, Lee, Nussbaum, Chamian, and Krueger (2004) is the same as our net-dominance-metric that aggregates the information provided by our dominance-metric in Equation 2 of Cherchye and Vermeulen (2006). This note is to acknowledge the priority of the work by Wittkowski and his coauthors of which the present authors had unfortunately not been aware.
Postembryonic RNAi in Heterorhabditis bacteriophora: a nematode insect parasite and host for insect pathogenic symbionts
Authors: Ciche Todd A , Sternberg Paul W 
Published: September 2007

Abstract
Background
Heterorhabditis bacteriophora is applied throughout the world for the biological control of insects and is an animal model to study interspecies interactions, e.g. mutualism, parasitism and vector-borne disease. H. bacteriophora nematodes are mutually associated with the insect pathogen, Photorhabdus luminescens. The developmentally arrested infective juvenile (IJ) stage nematode (vector) specifically transmits Photorhabdus luminescens bacteria (pathogen) in its gut mucosa to the haemocoel of insects (host). The nematode vector and pathogen alone are not known to cause insect disease. RNA interference is an excellent reverse genetic tool to study gene function in C. elegans, and it would be useful in H. bacteriophora to exploit the H. bacteriophora genome project, currently in progress.

Results
Soaking L1 stage H. bacteriophora with seven dsRNAs of genes whose C. elegans orthologs had severe RNAi phenotypes resulted in highly penetrant and obvious developmental and reproductive abnormalities. The efficacy of postembryonic double strand RNA interference (RNAi) was evident by abnormal gonad morphology and sterility of adult H. bacteriophora and C. elegans presumable due to defects in germ cell proliferation and gonad development. The penetrance of RNAi phenotypes in H. bacteriophora was high for five genes (87–100%; Hba-cct-2, Hba-daf-21, Hba-icd-1; Hba-nol-5, and Hba-W01G7.3) and moderate for two genes (usually 30–50%; Hba-rack-1 and Hba-arf-1). RNAi of three additional C. elegans orthologs for which RNAi phenotypes were not previously detected in C. elegans, also did not result in any apparent phenotypes in H. bacteriophora. Specific and severe reduction in transcript levels in RNAi treated L1s was determined by quantitative real-time RT-PCR. These results suggest that postembryonic RNAi by soaking is potent and specific.

Conclusion
Although RNAi is conserved in animals and plants, RNAi using long dsRNA is not. These results demonstrate that RNAi can be used effectively in H. bacteriophora and can be applied for analyses of nematode genes involved in symbiosis and parasitism. It is likely that RNAi will be an important tool for functional genomics utilizing the high quality draft H. bacteriophora genome sequence.
Gene sequence variations of the platelet P2Y12 receptor are associated with coronary artery disease
Authors: Cavallari Ugo , Trabetti Elisabetta , Malerba Giovanni , Biscuola Michele , Girelli Domenico , Olivieri Oliviero , Martinelli Nicola , Angiolillo Dominick J , Corrocher Roberto , Pignatti Pier Franco 
Published: September 2007

Abstract

Background
The platelet P2Y12 receptor plays a key role in platelet activation. The H2 haplotype of the P2Y12 receptor gene (P2RY12) has been found to be associated with maximal aggregation response to adenosine diphosphate (ADP) and with increased risk for peripheral arterial disease. No data are available on its association with coronary artery disease (CAD).

Methods
The H2 haplotype of the P2RY12 was determined in 1378 unrelated patients of both sexes selected according to the presence of significant coronary artery disease (CAD group) or having normal coronary angiogram at cardiac catheterization (CAD-free group). Significant coronary artery disease was angiographically determined, and was defined as a greater than 50% visually estimated luminal diameter stenosis in at least one major epicardial coronary artery.

Results
In the studied population 71.9% had CAD (n = 991) and 28.1% had normal coronary angiogram (n = 387). H2 haplotype carriers were more frequent in the CAD group (p = 0.03, OR = 1.36, 95%CI = 1.02–1.82). The H2 haplotype was significantly associated with CAD in non-smokers (p = 0.007, OR = 1.83 95%CI = 1.17–2.87), but not in smokers. The association remained significant after adjustment for other covariates (age, triglycerides, HDL, hypertension, diabetes) by multivariate logistic regression (p = 0.004, OR = 2.32 95%CI = 1.30–4.15).

Conclusion
Gene sequence variations of the P2Y12 receptor gene are associated with the presence of significant CAD, particularly in non-smoking individuals.
The effects of ProAlgaZyme novel algae infusion on metabolic syndrome and markers of cardiovascular health
Authors: Oben Julius , Enonchong Ebangha , Kuate Dieudonne , Mbanya Dora , Thomas Tiffany C. , Hildreth DeWall J. , Ingolia Thomas D. , Tempesta Michael S. 
Published: September 2007

Abstract

Background
Metabolic Syndrome, or Syndrome X, is characterized by a set of metabolic and lipid imbalances that greatly increases the risk of developing diabetes and cardiovascular disease. The syndrome is highly prevalent in the United States and worldwide, and treatments are in high demand. ProAlgaZyme, a novel and proprietary freshwater algae infusion in purified water, has been the subject of several animal studies and has demonstrated low toxicity even with chronic administration at elevated doses. The infusion has been used historically for the treatment of several inflammatory and immune disorders in humans and is considered well-tolerated. Here, the infusion is evaluated for its effects on the cardiovascular risk factors present in metabolic syndrome in a randomized double-blind placebo-controlled study involving 60 overweight and obese persons, ages 25–60. All participants received four daily oral doses (1 fl oz) of ProAlgaZyme (N = 22) or water placebo (N = 30) for a total of 10 weeks, and were encouraged to maintain their normal levels of physical activity. Blood sampling and anthropometric measurements were taken at the beginning of the study period and after 4, 8 and 10 weeks of treatment. Eight participants did not complete the study.

Results
ProAlgaZyme brought about statistically significant (p < 0.001) reductions in the following: weight, body fat, total cholesterol, LDL-cholesterol, triglycerides, C-reactive protein and fasting blood glucose levels, accompanied by a significant (p < 0.001) increase in HDL-cholesterol levels over the 10-week study period. The infusion was well-tolerated and no side effects were noted.

Conclusion
ProAlgaZyme (4 fl oz daily) consumption resulted in significant reductions in weight and blood glucose levels, while significantly improving serum lipid profiles and reducing markers of inflammation, thus improving cardiovascular risk factors in overweight and obese subjects over a course of 10 weeks with an absence of adverse side effects.

Trial Registration
US ClinicalTrials.gov NCT00489333
Primary colorectal small cell carcinoma: A clinicopathological and immunohistochemical study of 10 cases
Authors: El Demellawy Dina , Khalifa Mahmoud A , Ismiil Nadia , Wong Shun , Ghorab Zeina 
Published: September 2007

Abstract
Colorectal small cell carcinoma (SmCC) is a rare tumor with an aggressive course. The aim of this study is to summarize our experience with this tumor and to highlight its immunohistochemical profile. Ten cases of colorectal SmCC were identified in our files and a panel of immunostains was performed. Follow up was available for the average of 3 years, during which 7 patients died and 3 were alive with disease. All cases were positive for LMWK, CK 19 and pancytokeratin but were negative for TTF-1 and CA 125. EGFR was positive in 7 cases. TTF-1 negative staining may be valuable in differentiating it from its pulmonary counterpart. CDX2, mCEA, CD56, synaptophysin, NSE and chromogranin can help differentiate it from non-endocrine poorly differentiated adenocarcinoma. The expression of EGFR in a subset of patients has not been reported earlier and has to be evaluated in larger series to assess its role in the planning of targeted biologic therapy.
Cross-species cluster co-conservation: a new method for generating protein interaction networks
Authors: Karimpour-Fard Anis , Detweiler Corrella S , Erickson Kimberly D , Hunter Lawrence , Gill Ryan T 
Published: September 2007

AbstractCo-conservation (phylogenetic profiles) is a well-established method for predicting functional relationships between proteins. Several publicly available databases use this method and additional clustering strategies to develop networks of protein interactions (cluster co-conservation (CCC)). CCC has previously been limited to interactions within a single target species. We have extended CCC to develop protein interaction networks based on co-conservation between protein pairs across multiple species, cross-species cluster co-conservation.
Accelerated wound healing in leukocyte-specific, protein 1-deficient mouse is associated with increased infiltration of leukocytes and fibrocytes
Authors: Wang JianFei , Jiao Haiyan , Stewart Tara L , Lyons Megan V H , Shankowsky Heather A , Scott Paul G , Tredget Edward E 
Published: September 2007

AbstractWound healing is a complex process involving the integrated actions of numerous cell types, soluble mediators, and ECM. Recently, a newly identified cell type, the fibrocyte, has been reported to contribute to wound healing and fibrotic conditions such as hypertrophic scarring. We previously established leukocyte-specific protein 1 (LSP1) as a marker for fibrocytes. LSP1 is an F-actin binding protein and substrate of p38 mitogen-activated protein kinase and protein kinase C, and has been reported to be important in leukocyte chemotaxis. We examine the biological roles of LSP1 in skin wound healing using Lsp1−/− null mice. These animals showed accelerated healing of full-thickness skin wounds, with increased re-epithelialization rates, collagen synthesis, and angiogenesis. Healing wounds in Lsp1−/− mice had higher densities of neutrophiles, macrophages, and fibrocytes. Along with increased leukocyte infiltration, levels of macrophage-derived chemokine expression, TGF-β1, and VEGF were all up-regulated. These results demonstrate that the absence of LSP1 promotes healing of skin wounds. The primary mechanism seems to be an increase in leukocyte infiltration, leading to locally elevated synthesis and release of chemokines and growth factors. Further analysis of Lsp1−/− mice may suggest ways to improve wound healing and/or treat fibrotic conditions of skin and other tissue.
Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy
Authors: Symmans W. Fraser , Peintinger Florentia , Hatzis Christos , Rajan Radhika , Kuerer Henry , Valero Vicente , Assad Lina , Poniecka Anna , Hennessy Bryan , Green Marjorie , Buzdar Aman U. , Singletary S. Eva , Hortobagyi Gabriel N. , Pusztai Lajos 
Published: September 2007

Purpose To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response. Patients and Methods Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses. Results RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort. Conclusion RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.
Phase II Pethema Trial of Alternating Bortezomib and Dexamethasone As Induction Regimen Before Autologous Stem-Cell Transplantation in Younger Patients With Multiple Myeloma: Efficacy and Clinical Implications of Tumor Response Kinetics
Authors: Rosiñol Laura , Oriol Albert , Mateos Maria Victoria , Sureda Anna , García-Sánchez Pedro , Gutiérrez Norma , Alegre Adrián , Lahuerta Juan José , de la Rubia Javier , Herrero Carlos , Liu Xiangyang , Van de Velde Helgi , San Miguel Jesús , Bladé Joan 
Published: September 2007

Purpose This is the first study in which bortezomib and dexamethasone were administered on an alternating basis as up-front therapy in multiple myeloma (MM). We investigated the efficacy and kinetics of response to each drug and safety. Patients and Methods Patients with newly diagnosed MM who were less than 66 years old were treated with bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 (cycles 1, 3, and 5) and dexamethasone 40 mg orally on days 1 through 4, 9 to 12, and 17 to 20 (cycles 2, 4, and 6), followed by autologous stem-cell transplantation (ASCT). Responses were evaluated by modified European Bone Marrow Transplantation criteria. Random effects models were used to analyze the tumor response kinetics. Results Forty patients were enrolled. Partial response (PR) or greater was 65% (12.5% complete response [CR], 10% very good PR [VGPR], and 42.5% PR) plus 17.5% minor response. Time to response was rapid, with 82% serum M-protein reduction achieved within the first two cycles. The M-protein decrease was similar with dexamethasone and with bortezomib (P = .48). Chromosome 13 deletion, t(4;14), and t(14;16) did not have a negative impact on response. Toxicity was low, with no grade 3 to 4 peripheral neuropathy and no grade 2 to 4 thrombocytopenia. The response rate after ASCT was 88%, with 33% CR (negative immunofixation) plus 22% VGPR. Conclusion Bortezomib alternating with dexamethasone is a highly effective induction regimen with low toxicity. The kinetic study has shown a high degree of heterogeneity in response and rapid effect from both agents, supporting the use of a short induction regimen before ASCT in MM.
Identification of a Polycystic Ovary Syndrome Susceptibility Variant in Fibrillin-3 and Association with a Metabolic Phenotype
Authors: Urbanek Margrit , Sam Susan , Legro Richard S. , Dunaif Andrea 
Published: September 2007

Abstract
Context: Polycystic ovary syndrome (PCOS), the most common reproductive endocrine disorder of premenopausal women, is also associated with metabolic abnormalities including insulin resistance and an increased risk for diabetes mellitus. We previously mapped a PCOS susceptibility locus to chromosome 19p13.2 near the dinucleotide repeat marker D19S884.
Objective: Our objective is to localize the chromosome 19p13.2 PCOS susceptibility locus and determine its impact on metabolic features of PCOS.
Design: Resequencing and family-based association testing were used to examine the effect of sequence variation within 100 kb of D19S884 on the reproductive and metabolic phenotypes of PCOS.
Setting: The study was conducted in an academic medical center.
Subjects: Genetic analyses were performed on DNA obtained from1723 individuals in 412 families with 412 index cases and 43 affected sisters of predominantly European origin (&gt;94%). Genotype-phenotype associations were assessed in 601 women with PCOS and 168 brothers of affected women.
Results: D19S884 allele 8 (A8) within intron 55 of the fibrillin-3 (FBN3) gene showed the strongest evidence for association with PCOS of 53 variants tested (Pcorrected = 0.0037). A8 was also associated with higher levels of fasting insulin and homeostasis model assessment for insulin resistance in women with PCOS and higher fasting levels of proinsulin and proinsulin/insulin ratio in brothers.
Conclusions: These findings strongly suggest that A8 of D19S884 is the chromosome 19p13.2 PCOS susceptibility locus. The association of D19S884 with markers of insulin resistance and pancreatic β-cell dysfunction suggests that the same variant contributes to the reproductive and metabolic abnormalities of PCOS in affected women and their brothers.