bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endometrial Profile of Tamoxifen and Low-Dose Estradiol Combination Therapy
Authors: Wood Charles E. , Kaplan Jay R. , Fontenot M. Babette , Williams J. Koudy , Cline J. Mark 
Published: January 2010

AbstractPurpose: Combination estrogen + progestin therapy has been associated with increased breast cancer risk in postmenopausal women. Selective estrogen receptor modulators (SERM) are potential alternatives to progestins, although the endometrial safety of estrogen + SERM co-therapies is not known. The goal of this study was to evaluate the endometrial profile of low-dose estradiol and the SERM tamoxifen alone and in combination.Experimental Design: Twenty-four postmenopausal female cynomolgus macaques were randomized by social group to receive placebo, low-dose micronized estradiol (E2; 0.25 mg/1,800 kcal), the SERM tamoxifen (Tam; 20 mg/1,800 kcal), or E2 + Tam for 4 months in a parallel-arm design.Results: Tamoxifen alone resulted in overlapping but distinct effects compared with E2. Both E2 and Tam increased uterine weight and endometrial thickness, whereas only E2 increased endometrial proliferation. Morphologic effects were similar for Tam and E2 + Tam, which both induced stromal fibrosis and cystic change. Tamoxifen inhibited E2-induced proliferation and expression of genes related to cell cycle progression while exhibiting mixed agonist and antagonist effects on gene markers of estrogen receptor activity. The gene expression profile for E2 + Tam was distinct from either E2 or Tam alone but dominated by the Tam effect for estrogen-regulated genes. Tam also attenuated E2 effects on both vaginal maturation and cervical epithelial height.Conclusions: These findings characterize a novel phenotype resulting from estrogen + SERM co-therapy. The predominance of Tam effects on endometrial proliferation, morphology, and transcriptional profiles suggests that endometrial risks for E2 + Tam may be similar to Tam alone. Clin Cancer Res; 16(3); 946–56
Spatial Analyses Identify the Geographic Source of Patients at a National Cancer Institute Comprehensive Cancer Center
Authors: Su Shu-Chih , Kanarek Norma , Fox Michael G. , Guseynova Alla , Crow Shirley , Piantadosi Steven 
Published: January 2010

Abstract
Purpose: We examined the geographic distribution of patients to better understand the service area of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, a designated National Cancer Institute (NCI) comprehensive cancer center located in an urban center. Like most NCI cancer centers, the Sidney Kimmel Comprehensive Cancer Center serves a population beyond city limits. Urban cancer centers are expected to serve their immediate neighborhoods and to address disparities in access to specialty care. Our purpose was to learn the extent and nature of the cancer center service area.
Experimental Design: Statistical clustering of patient residence in the continental United States was assessed for all patients and by gender, cancer site, and race using SaTScan.
Results: Primary clusters detected for all cases and demographically and tumor-defined subpopulations were centered at Baltimore City and consisted of adjacent counties in Delaware, Pennsylvania, Virginia, West Virginia, New Jersey and New York, and the District of Columbia. Primary clusters varied in size by race, gender, and cancer site. Spatial analysis can provide insights into the populations served by urban cancer centers, assess centers' performance relative to their communities, and aid in developing a cancer center business plan that recognizes strengths, regional utility, and referral patterns.
Conclusions: Today, 62 NCI cancer centers serve a quarter of the U.S. population in their immediate communities. From the Baltimore experience, we might project that the population served by these centers is actually more extensive and varies by patient characteristics, cancer site, and probably cancer center services offered. Clin Cancer Res; 16(3); 1065–72
Application of a Time-Varying Covariate Model to the Analysis of CA 19-9 as Serum Biomarker in Patients with Advanced Pancreatic Cancer
Authors: Boeck Stefan , Haas Michael , Laubender Rüdiger P. , Kullmann Frank , Klose Christina , Bruns Christiane J. , Wilkowski Ralf , Stieber Petra , Holdenrieder Stefan , Buchner Hannes , Mansmann Ulrich , Heinemann Volker 
Published: January 2010

Abstract
Purpose: The clinical relevance of CA 19-9 as surrogate biomarker in advanced pancreatic cancer is a matter of debate.
Experimental Design: This retrospective multicenter study included patients with histologically confirmed advanced pancreatic cancer treated with first-line therapy. Analysis of CA 19-9 was done using the Elecsys assay (Roche Diagnostics). For an analysis of CA 19-9 kinetics, at least three measurements during first-line chemotherapy had to be available. The effect of pretreatment CA 19-9 levels on time-to-progression (TTP) and overall survival (OS) was modeled by Cox proportional hazards regression. The effect of CA 19-9 kinetics was also modeled by Cox proportional hazards regression where CA 19-9 was treated as a time-varying covariate.
Results: One hundred and fifteen patients from five German centers were included; 73% of them were treated within prospective clinical trials. Median TTP was 4.4 months and median OS was 9.4 months; univariate analysis indicated that pretreatment CA 19-9 [as continuous variable, log (CA 19-9)] was significantly associated with TTP [hazard ratio (HR), 1.24; P &lt; 0.001] and OS (HR, 1.16; P = 0.002). These associations remained significant within multivariate analysis. For CA 19-9 kinetics during chemotherapy, data from 69 patients (TTP) and 84 patients (OS) were available, respectively; log (CA 19-9) kinetics after start of treatment were found to be a significant predictor for TTP in univariate (HR, 1.48; P &lt; 0.001) and multivariate (HR, 1.45; P &lt; 0.001) analyses, and also for OS (univariate: HR, 1.34; P &lt; 0.001; multivariate: HR, 1.38; P &lt; 0.001).
Conclusion: Pretreatment CA 19-9 and CA 19-9 kinetics may serve as a useful serum biomarker in advanced pancreatic cancer. Clin Cancer Res; 16(3); 986–94
Immunobiological Characterization of Cancer Stem Cells Isolated from Glioblastoma Patients
Authors: Di Tomaso Tiziano , Mazzoleni Stefania , Wang Ena , Sovena Gloria , Clavenna Daniela , Franzin Alberto , Mortini Pietro , Ferrone Soldano , Doglioni Claudio , Marincola Francesco M. , Galli Rossella , Parmiani Giorgio , Maccalli Cristina 
Published: January 2010

Abstract
Purpose: Cancer stem cells (CSC) have been isolated from human tumors, including glioblastoma multiforme (GBM). The aims of this study were the immunobiological characterization of GBM CSCs and the assessment of whether these cells represent suitable targets for immunotherapy.
Experimental Design: GBM CSC lines and their fetal bovine serum (FBS)–cultured non-CSC pair lines were generated and examined by flow cytometry for expression of known tumor antigens, MHC-I and MHC-II molecules, antigen-processing machinery components, and NKG2D ligands. In addition, immunogenicity and immunosuppression of such cell lines for autologous or allogeneic T lymphocytes were tested by cytokine secretion (ELISPOT) or proliferation (carboxyfluorescein diacetate succinimidyl ester) assays, respectively.
Results: Both GBM CSC and FBS lines were weakly positive and negative for MHC-I, MHC-II, and NKG2D ligand molecules, respectively. Antigen-processing machinery molecules were also defective in both cell types. Upregulation of most molecules was induced by IFNs or 5-Aza deoxycytidine, although more efficiently in FBS than in CSCs. Patient T-cell responses, mediated by both TH1 and the TH2 subsets, against autologous CSC could be induced in vitro. In addition, CSC but not their paired FBS tumor lines inhibited T-cell proliferation of healthy donors. Notably, a differential gene signature that was confirmed at the protein levels for some immunologic-related molecules was also found between CSC and FBS lines.
Conclusions: These results indicate lower immunogenicity and higher suppressive activity of GBM CSC compared with FBS lines. The immunogenicity, however, could be rescued by immune modulation leading to anti-GBM T cell–mediated immune response. Clin Cancer Res; 16(3); 800–13
A Fine-Needle Aspirate–Based Vulnerability Assay Identifies Polo-Like Kinase 1 as a Mediator of Gemcitabine Resistance in Pancreatic Cancer
Authors: Jimeno Antonio , Rubio-Viqueira Belen , Rajeshkumar N.V. , Chan Audrey , Solomon Anna , Hidalgo Manuel 
Published: January 2010

AbstractThis work aimed to discover targets for combination treatment with gemcitabine in pancreatic cancer. We selected 11 tumors from our live collection of freshly generated pancreatic cancer xenografts with known degrees of varying gemcitabine sensitivity. We briefly (6 h) exposed fine-needle aspiration material to control vehicle or gemcitabine (1 μmol/L) and compared the gene expression of the treated and untreated samples using a reverse transcription-PCR–based, customized low-density array with 45 target genes of therapeutic interest. The gene expression of the untreated sample (which can be considered a baseline/static readout) was not predictive of gemcitabine efficacy in these tumors. Altogether, the only gene that differentiated sensitive versus resistant cases was polo-like kinase 1 (Plk1), showing &gt;50% downregulation in sensitive cases and no change in the resistant cases. Inhibition of Plk1 by either small interfering RNA gene knockdown or with the Plk1 pathway modulator (ON 01910.Na) synergized with gemcitabine in gemcitabine-refractory in vitro models providing mechanistic proof of concept. In vivo experiments in gemcitabine-resistant xenografts showed synergistic activity decreasing cell proliferation and tumor regressions. A quantitative gene expression–based vulnerability assay identified Plk1 as a relevant target dictating the susceptibility of pancreatic cancer to gemcitabine. Dynamic interrogation of cancer has the potential to provide key information about mechanisms of resistance and to enhance individualization of treatment. Mol Cancer Ther; 9(2); 311–8
Chemoprevention of B-Cell Lymphomas by Inhibition of the Myc Target Spermidine Synthase
Authors: Forshell TachaZi Plym , Rimpi Sara , Nilsson Jonas A. 
Published: January 2010

Abstract
The oncogenic transcription factor c-Myc (Myc) is frequently overexpressed in human cancers. Myc is known to induce or repress a large set of genes involved in cell growth and proliferation, explaining the selection for mutations in cancer that deregulate Myc expression. Inhibition of ornithine decarboxylase, an enzyme of the polyamine biosynthetic pathway and a Myc target, has been shown to be chemopreventive. In the present study, we have dissected the role of another enzyme in the polyamine biosynthetic pathway, spermidine synthase (Srm), in Myc-induced cancer. We find that Srm is encoded by a Myc target gene containing perfect E-boxes and that it is induced by Myc in a direct manner. RNA interference against Srm shows that it is important for Myc-induced proliferation of mouse fibroblasts but to a lesser extent for transformation. Using the compound trans-4-methylcyclohexylamine, we show that Srm inhibition can delay the onset of B-cell lymphoma development in λ-Myc transgenic mice. We therefore suggest that inhibition of Srm is an additional chemopreventive strategy that warrants further consideration. Cancer Prev Res; 3(2); 140–7
Cancer Chemoprevention Locks onto a New Polyamine Metabolic Target
Authors: Gerner Eugene W. 
Published: January 2010

Abstract
Ornithine decarboxylase has a relatively long history as a target for cancer chemoprevention and chemotherapy. Plym Forshell et al. report new evidence (beginning on p. 140 in this issue of the journal) indicating that spermidine synthase, a fellow enzyme of ornithine decarboxylase in polyamine metabolism, is transactivated in part by the MYC gene and is a potential target for chemoprevention of B-cell lymphomas. Cancer Prev Res; (3)2; 125–7
Assessing Efficacy in Early-Phase Cancer Prevention Clinical Trials: The Case of Ki-67 in the Lung
Authors: Szabo Eva 
Published: January 2010

AbstractThis perspective on Kim et al. (beginning on p. 148 in this issue of the journal) examines the value of the Ki-67 proliferation index as a surrogate end point in early-phase clinical lung cancer prevention trials. The clinical trial of Kim et al. shows an effect of the cyclooxygenase-2–selective inhibitor celecoxib at a high dose on Ki-67 expression in the normal bronchial epithelia of current and former smokers. The critical issue of how these data can be used to further drug development is discussed. Cancer Prev Res; 3(2); 128–31
A Culturally Focused Exercise Program in Hispanic Adults With Type 2 Diabetes
Authors: Martyn-Nemeth Pamela A. , Vitale Gail A. , Cowger Debra R. 
Published: January 2010

Purpose The purpose of this pilot study was to examine the feasibility and effectiveness of a community-based, culturally focused, exercise program for adults in the Hispanic community with type 2 diabetes. Methods A pretest/posttest design using a culturally designed exercise program through dance was used. A total of 19 Mexican American men and women (39 to 64 years of age) with type 2 diabetes were recruited. Mean preprogram and postprogram differences were examined in hemoglobin A1C, lipid panel, body mass index (BMI), and psychological well-being. Results Feasibility was demonstrated by exceeding our recruitment goal and achieving an 84% completion rate and 75% attendance rate for the exercise sessions. Mean hemoglobin A1C, lipids, and psychological well-being demonstrated trends toward improvement from the beginning of the program to the end. BMI remained unchanged. Physical activity increased and all participants met the physical activity goals from the national physical activity guidelines for Americans by the end of the program. Conclusions The culturally focused exercise program detailed here is effective in promoting regular physical activity among Hispanic adults with type 2 diabetes.
Fish Oil-induced Yellow Fat Disease in Rats. III. Lipolysis in Affected Adipose Tissue
Authors: Danse L. H. J. C. , Verschuren P. M. 
Published: January 2010

Basal and hormone-stimulated lipolysis of adipose tissue was measured at successive stages during the development of fish oil-induced yellow fat disease in rats. Changes of lipolytic activity at an early stage of yellow fat disease were not seen. There was a significant increase of basal lipolysis and a decrease of stimulated lipolysis when many fat cells were affected (stage E). Since the increased basal lipolysis probably originates from degenerated fat cells, the mechanism of enzyme activation is not clear. The decreased stimulated lipolysis was proportional to the number of affected fat cells and resulted from membrane damage of these cells. Increased 5-nucleotidase activity, seen in affected fat cells, may be important, to this reduced stimulated lipolysis.
Retinal Dysplasia of English Springer Spaniel Dogs: Light Microscopy of the Postnatal Lesions
Authors: Toole D. O. , Young S. , Severin G. A. , Neumann S. 
Published: January 2010

The histologic features of retinal dysplasia were studied in 26 English springer spaniel dogs of one day to four years of age. Dysplastic lesions in neonatal pups occurred predominantly in the peripapillary tapetal area of sensory retina. They consisted of complex linear folds and rosettes which were composed of hyperplastic neuroblasts. Dysplasia usually was not associated with incomplete differentiation of the outer neuroblastic layer. The outer limiting membrane was absent locally and numerous patent subretinal capillaries existed in the region of folds. The dysplastic features may be related to aberrant development of Muller cells and of retinal capillaries. In adolescent dogs, dysplastic lesions were less complex and usually were not accompanied by aberrant capillaries. Focal or complete retinal separation was present in some adolescent dogs. In adult dogs, features of retinal atrophy were found within dysplastic areas. No significant histologic lesions were found in the extraocular tissues of 12 affected dogs which were surveyed extensively.
Morphologic Changes Following Intraarticular Inoculation of Mycoplasma bovis in Calves
Authors: Ryan M. J. , Wyand D. S. , Hill D. L. , Tourtellotte M. E. , Yang T. J. 
Published: January 2010

Intraarticular inoculation of Mycoplasma bovis into the joints of six-week-old calves caused severe arthritis in five inoculates and mild arthritis in a sixth. Intraarticular inoculation of killed M. bovis did not cause arthritis. Arthritic calves had fever, joint swelling, lameness, neutrophilia, and intercurrent pneumonia from which M. bovis could not be recovered. Gross lesions were massive fibrinosuppurative synovitis and tenosynovitis, erosion of cartilage, and its replacement by polypoid granulation tissue. Histologic lesions were extensive ulceration of synovial membranes, leukocytic infiltration of the suhsynovium, congestion, hyperemia, and thrombosis of the subsynovial vessels. Cartilage erosion was accompanied by chronic osteomyelitis and formation of pannus tissue. The presence of thrombi and platelet aggregates suggests that the inflammatory process in the synovium may arise from the interaction of M. bovis with the vasculature and the coagulation process of the host.
Malignant Mesothelioma in Urban Dogs
Authors: Harbison M. L. , Godleski J. J. 
Published: January 2010

Clinical and postmortem materials from six dogs with a diagnosis of malignant mesothelioma were studied retrospectively. The dogs were urban pets with clinical signs of malignant effusions. Two mesotheliomas were pleural, one pericardial, and one peritoneal. Both pleura and pericardium were involved in one dog, and the pleura and peritoneum in another. On gross examination at necropsy, diffuse granular or velvety plaques covering mesothelial surfaces were found in all dogs; firm discrete pleural nodules also were present in two dogs. Neither distant mestastases nor areas of deep lung invasion were found. The tumors varied histologically, but the most common type was epithelial with a papillary pattern. Ultrastructurally, the neoplastic cells had prominent surface microvilli, numerous desmosomes, and tonofilaments. Lung tissue from these dogs and from control dogs was evaluated for the presence of ferruginous bodies. Asbestos bodies were found in three of five dogs with mesotheliomas but rarely were found in control dogs. As a group, the mesothelioma cases had significantly more asbestos bodies and total ferruginous bodies than controls. The clinical and morphologic appearance of canine mesothelioma is similar to human mesothelioma and also may be associated with exposure to airborne fibers.
NFAT pulls the strings during CD4+ T helper cell effector functions
Authors: Hermann-Kleiter Natascha , Baier Gottfried 
Published: January 2010

Abstract
The Ca2+ dependent transcription factor family known as nuclear factor of activated T cells (NFAT) has been shown to be important in T-cell immune responses. Because NFAT proteins have a weak DNA-binding capacity, they cooperate with other transcription factors at composite sites within the promoters of target genes. Recently, NFAT was shown to also be important for the induction of specific genetic programs that guide the differentiation and effector or regulatory activities of CD4+ T helper subsets via the transcriptional regulation of their lineage-specific transcription factors, specifically T-bet (Th1), Gata3 (Th2), RORγt (Th17), and Foxp3 (iTregs). In addition, the NFAT family governs the transcription of several signature cytokines, including their cytokine receptors. Subsequently, the integration of these complex intracellular signal transduction cascades is considered to critically determine the crosstalk between the T-cell receptor and receptors that are activated by both the adaptive and innate immune systems to determine pathways of T helper cell differentiation and function. Here, we carefully review the critical role of the established transcriptional partners and functional outcomes of these NFAT interactions in regard to the effector responses of these clinically relevant CD4+ T helper subsets.
Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study
Authors: Löwenberg Bob , Beck Joachim , Graux Carlos , van Putten Wim , Schouten Harry C. , Verdonck Leo F. , Ferrant Augustin , Sonneveld Pieter , Jongen-Lavrencic Mojca , von Lilienfeld-Toal Marie , Biemond Bart J. , Vellenga Edo , Breems Dimitri , de Muijnck Hilde , Schaafsma Ron , Verhoef Gregor , Döhner Hartmut , Gratwohl Alois , Pabst Thomas , Ossenkoppele Gert J. , Maertens Johan ,   for the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON),   German Austrian AML Study Group (AMLSG),   Swiss Group for Clinical Cancer Research Collaborative Group (SAKK)
Published: January 2010

Abstract
In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m2 every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 × 109/L and neutrophils 0.5 × 109/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.