bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Oral Contraceptives on Sex Hormone-Binding Globulin and Androgen Levels: A Retrospective Study in Women with Sexual Dysfunction
Authors: Panzer Claudia , Wise Sarah , Fantini Gemma , Kang Dongwoo , Munarriz Ricardo , Guay Andre , Goldstein Irwin 
Published: January 2006

ABSTRACT

Introduction
Oral contraceptives (OCs) have been the preferred method of birth control because of their high rate of effectiveness. OC use, however, has been associated with women's sexual health complaints and androgen insufficiency. OC use is associated with a decrease of androgen ovarian synthesis and an increase in the production of sex hormone-binding globulin (SHBG). There have been limited studies assessing SHBG values after discontinuation of OC use.

Aim
To retrospectively investigate SHBG levels before and after discontinuation of OC use.

Main Outcome Measure
Sex hormone-binding globulin values were compared at baseline, while on the OC, and well beyond the 7-day half-life of SHBG at 49–120 (mean 80) days and &gt;120 (mean 196) days after discontinuation of OCs.

Methods
A total of 124 premenopausal women with sexual health complaints for &gt;6 months met inclusion/exclusion criteria. Three groups of women were defined: (i) “Continued-Users” (N = 62; mean age 32 years) had been on OCs for &gt;6 months and continued taking them; (ii) “Discontinued-Users” (N = 39; mean age 33 years) had been on OCs for &gt;6 months and discontinued them; and (iii) “Never-Users” (N = 23; mean age 36 years) had never taken OCs.

Results
Sex hormone-binding globulin values in the “Continued-Users” were four times higher than those in the “Never-User” group (mean 157 ± 13 nmol/L vs. 41 ± 4 nmol/L; P &lt; 0.0001). Despite a decrease in SHBG values after discontinuation of OC use, SHBG levels in “Discontinued-Users” remained elevated in comparison with “Never-Users” (N = 26; P &lt; 0.0001 for &gt;120 days).

Conclusion
In women with sexual dysfunction, SHBG changes in “Discontinued-Users” did not decrease to values consistent with “Never-Users.” Long-term sexual, metabolic, and mental health consequences might result as a consequence of chronic SHBG elevation. Does prolonged exposure to the synthetic estrogens of OCs induce gene imprinting and increased gene expression of SHBG in the liver in some women? Prospective research is needed.
Effective interventions for lifestyle change after myocardial infarction or coronary artery revascularization
Authors: Cobb Stephanie L. , Brown Debra J. , Davis Leslie L. 
Published: January 2006

AbstractPurpose: This science clinical paper reviews medical literature and examines interventions that are currently used to assist patients in achieving lifestyle change after myocardial infarction or coronary artery revascularization. Interventions that focused on both provider‐ and patient‐implemented strategies were included. The effectiveness of these interventions to significantly reduce coronary heart disease risk factors was explored.Data sources: Original longitudinal research studies or reviews indexed in PubMed between 1999 and 2004 were included. Eight studies were identified that met the inclusion criteria and presented successful interventions to increase participants’ adherence to recommended lifestyle changes.Conclusions: Current strategies for achieving recommended risk factor reductions include frequent follow‐up, intensive diet changes, individualized and group exercise, coaching, group meetings, education on lifestyle modification and behavior change, and formal cardiac rehabilitation programs.Implications for practice: Nurse Practitioners can help close the gap between evidence‐based recommendations and clinical practice by implementing education programs in their practices and in the community. Recommendations include frequent follow‐up visits, negotiating personalized treatment plans, and a general emphasis on therapeutic lifestyle change as an essential component of the treatment plan.
Interleukin-17 Receptor-Like Gene Is a Novel Antiapoptotic Gene Highly Expressed in Androgen-Independent Prostate Cancer
Authors: You Zongbing , Shi Xu-Bao , DuRaine Grayson , Haudenschild Dominik , Tepper Clifford G. , Hao Lo Su , Gandour-Edwards Regina , de Vere White Ralph W. , Reddi A. Hari 
Published: January 2006

Abstract
We have recently identified a new gene, interleukin-17 receptor-like (IL-17RL), which is expressed in normal prostate and prostate cancer. This investigation is focused on the role of IL-17RL in prostate cancer. We found that IL-17RL was expressed at significantly higher levels in several androgen-independent prostate cancer cell lines (PC3, DU145, cds1, cds2, and cds3) and tumors compared with the androgen-dependent cell lines (LNCaP and MLC-SV40) and tumors. In an in vivo model of human prostate tumor growth in nude mice (CWR22 xenograft model), IL-17RL expression in tumors was induced by androgen deprivation. The relapsed androgen-independent tumors expressed higher levels of IL-17RL compared with the androgen-dependent tumors. Overexpression of IL-17RL in tumor necrosis factor α (TNFα)–sensitive LNCaP cells inhibited TNFα-induced apoptosis by blocking activation of caspase-3 downstream to caspase-2 and caspase-8. Reciprocally, knocking down IL-17RL expression by small interfering RNA induced apoptosis in all the prostate cancer cell lines studied. Taken together, these results show that IL-17RL is a novel antiapoptotic gene, which may confer partially the property of androgen-independent growth of prostate cancer by promoting cell survival. Thus, IL-17RL is a potential therapeutic target in the treatment of prostate cancer. (Cancer Res 2006; 66(1): 175-83)
Identification of Potential Human Oncogenes by Mapping the Common Viral Integration Sites in Avian Nephroblastoma
Authors: Pajer Petr , Pečenka Vladimír , Králová Jarmila , Karafiát Vít , Průková Dana , Zemanová Zdena , Kodet Roman , Dvořák Michal 
Published: January 2006

Abstract
Gene deregulation is a frequent cause of malignant transformation. Alteration of the gene structure and/or expression leading to cellular transformation and tumor growth can be experimentally achieved by insertion of the retroviral genome into the host DNA. Retrovirus-containing host loci found repeatedly in clonal tumors are called common viral integration sites (cVIS). cVIS are located in genes or chromosomal regions whose alterations participate in cellular transformation. Here, we present the chicken model for the identification of oncogenes and tumor suppressor genes in solid tumors by mapping the cVIS. Using the combination of inverse PCR and long terminal repeat-rapid amplification of cDNA ends technique, we have analyzed 93 myeloblastosis-associated virus type 2–induced clonal nephroblastoma tumors in detail, and mapped &gt;500 independent retroviral integration sites. Eighteen genomic loci were hit repeatedly and thus classified as cVIS, five of these genomic loci have previously been shown to be involved in malignant transformation of different human cell types. The expression levels of selected genes and their human orthologues have been assayed in chicken and selected human renal tumor samples, and their possible correlation with tumor development, has been suggested. We have found that genes associated with cVIS are frequently, but not in all cases, deregulated at the mRNA level as a result of proviral integration. Furthermore, the deregulation of their human orthologues has been observed in the samples of human pediatric renal tumors. Thus, the avian nephroblastoma is a valid source of cancer-associated genes. Moreover, the results bring deeper insight into the molecular background of tumorigenesis in distant species. (Cancer Res 2006; 66(1): 78-86)
Inhibition of DNA Methyltransferase Activity Prevents Tumorigenesis in a Mouse Model of Prostate Cancer
Authors: McCabe Michael T. , Low Jonathan A. , Daignault Stephanie , Imperiale Michael J. , Wojno Kirk J. , Day Mark L. 
Published: January 2006

Abstract
Transcriptional silencing of tumor suppressor genes by DNA methylation plays an important role in tumorigenesis. These aberrant epigenetic modifications may be mediated in part by elevated DNA methyltransferase levels. DNA methyltransferase 1 (DNMT1), in particular, is overexpressed in many tumor types. Recently, we showed that Dnmt1 is transcriptionally regulated by E2F transcription factors and that retinoblastoma protein (pRb) inactivation induces Dnmt1. Based on these observations, we investigated regulation of Dnmt1 by polyomavirus oncogenes, which potently inhibit the pRb pocket protein family. Infection of primary human prostate epithelial cells with BK polyomavirus dramatically induced Dnmt1 transcription following large T antigen (TAg) translation and E2F activation. For in vivo study of Dnmt1 regulation, we used the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which expresses the SV40 polyomavirus early region, including TAg, under control of a prostate-specific promoter. Analysis of TRAMP prostate lesions revealed greatly elevated Dnmt1 mRNA and protein levels beginning in prostatic intraepithelial neoplasia and continuing through advanced prostate cancer and metastasis. Interestingly, when TRAMP mice were treated in a chemopreventive manner with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza), 0 of 14 mice developed prostate cancer at 24 weeks of age, whereas 7 of 13 (54%) control-treated mice developed poorly differentiated prostate cancer. Treatment with 5-aza also prevented the development of lymph node metastases and dramatically extended survival compared with control-treated mice. Taken together, these data suggest that Dnmt1 is rapidly activated by pRb pathway inactivation, and that DNA methyltransferase activity is required for malignant transformation and tumorigenesis. (Cancer Res 2006; 66(1): 385-92)
Interplay between Two Hormone-Independent Activation Domains in the Androgen Receptor
Authors: Callewaert Leen , Van Tilborgh Nora , Claessens Frank 
Published: January 2006

Abstract
The androgen receptor (AR) plays a key role in prostate cancer development, as well as its treatments, even for the hormone-refractory state. Here, we report that an earlier described lysine-to-arginine mutation at position 179 in AR leads to a more potent AR. We show that two activation domains (Tau-1 and Tau-5) are necessary and sufficient for the full activity of AR and the intrinsic activity of the AR-NTD. Two α-helices surrounding the Lys179 define the core of Tau-1, which can act as an autonomous activation function, independent of p160 coactivators. Furthermore, we show that although the recruitment of p160 coactivators is mediated through Tau-5, this event is attenuated by core Tau-1. This better definition of the mechanisms of action of both Tau-1 and Tau-5 is instrumental for the design of alternative therapeutic strategies against prostate cancer. (Cancer Res 2006; 66(1): 543-53)
Identification of the NKG2D Haplotypes Associated with Natural Cytotoxic Activity of Peripheral Blood Lymphocytes and Cancer Immunosurveillance
Authors: Hayashi Tomonori , Imai Kazue , Morishita Yukari , Hayashi Ikue , Kusunoki Yoichiro , Nakachi Kei 
Published: January 2006

Abstract
We have previously shown that natural cytotoxic activity of peripheral blood lymphocytes was inversely related to cancer development based on a prospective cohort study. The genetic fraction of cytotoxic activity needs to be clarified, identifying individuals immunogenetically susceptible to cancer. A case-control study within the cohort members was designed: 102 cancer cases with peripheral lymphocyte DNA available and three control groups, each of which consisted of 204 subjects with each tertile level of cytotoxic activity. We first compared two control groups with high and low cytotoxic activity in terms of the single nucleotide polymorphisms in the natural killer complex gene region on chromosome 12p, identifying the haplotype alleles that were associated with the activity. Next, cancer risks were assessed for these haplotypes. We found two haplotype blocks, each of which generated two major haplotype alleles: low-activity-related LNK1 (frequency 0.478 and 0.615 in groups with high and low activity, respectively; P &lt; 0.00008) and high-activity-related HNK1 (0.480 and 0.348; P &lt; 0.0001), LNK2 (0.711 and 0.821; P &lt; 0.0002), and HNK2 (0.272 and 0.174; P &lt; 0.0008). These NKG2D haplotype alleles showed a significant difference between cases (0.632 for LNK1 and 0.333 for HNK1) and controls (0.554 for LNK1 and 0.406 for HNK1). The haplotype HNK1/HNK1 revealed a decreased risk of cancer (odds ratio, 0.471; 95% confidence interval, 0.233-0.952) compared with LNK1/LNK1. Individuals who are genetically predisposed to have low or high natural cytotoxic activity can in part be determined by NKG2D haplotyping, which in turn reveals an increased or decreased risk of cancer development. (Cancer Res 2006; 66(1): 563-70)
Characterization of Common UGT1A8, UGT1A9, and UGT2B7 Variants with Different Capacities to Inactivate Mutagenic 4-Hydroxylated Metabolites of Estradiol and Estrone
Authors: Thibaudeau Jean , Lépine Johanie , Tojcic Jelena , Duguay Yannick , Pelletier Georges , Plante Marie , Brisson Jacques , Têtu Bernard , Jacob Simon , Perusse Louis , Bélanger Alain , Guillemette Chantal 
Published: January 2006

AbstractThe oxidative metabolism of estrone (E1) and estradiol (E2) to form carcinogenic 4-hydroxy-catecholestrogens (4-OHCE) is associated with uterine and breast carcinogenesis. In this study, we conducted functional analyses of genetic variants in the UDP-glucuronosyltransferase UGT1A8, UGT1A9, and UGT2B7 enzymes primarily involved in the inactivation of 4-OHCEs. Compared with UGT2B7*2 (H268Y), UGT2B7*1 exhibited a 2-fold lower efficiency (intrinsic clearance) at conjugating 4-hydroxyestrone and 4-hydroxyestradiol at positions 3 and 4 caused by altered capacities (Vmax) and affinities (Km). The −79 G&gt;A promoter variation, characterizing the UGT2B7*2g haplotype, leads to a 50% reduction of transcription (P &lt; 0.001) in human endometrial carcinoma-1B cells. Furthermore, a &gt;12-fold decreased intrinsic clearance of the *1 proteins was induced by selected amino acid substitutions in UGT1A8 (*3 C277Y) and UGT1A9 (*3 M33T). Frequencies of the low-activity alleles in Caucasians were 45% for UGT2B7*1, 5% for the −79A promoter variant, 1.2% for UGT1A8*3, and 2.2% for UGT1A9*3. Supporting a protective role in two organs sensitive to 4-OHCE–induced damages, the expression of UGT enzymes was shown by immunohistochemistry in normal breast and endometrial tissues and confirmed by Western blotting in a subset of samples. Altogether, findings suggest that specific polymorphisms in UGT genes may modulate the exposure to carcinogenic metabolites of E2 and potentially lead to an altered risk of breast and endometrial cancers in women carrying the variant alleles. (Cancer Res 2006; 66(1): 125-33)
Histone Deacetylase Inhibitors Modulate the Sensitivity of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Resistant Bladder Tumor Cells
Authors: Earel James K. , VanOosten Rebecca L. , Griffith Thomas S. 
Published: January 2006

AbstractUrothelial carcinoma of the bladder accounts for ∼5% of all cancer deaths in humans. The large majority of tumors are superficial at diagnosis and, after local surgical therapy, have a high rate of local recurrence and progression. Current treatments extend time to recurrence but do not alter disease survival. The objective of the present study was to investigate the tumoricidal potential of combining the apoptosis-inducing protein tumor necrosis factor–related apoptosis inducing ligand (TRAIL) with histone deacetylase inhibitors (HDACi) against TRAIL-resistant bladder tumor cells. Pretreatment with HDACi at nontoxic doses, followed by incubation with TRAIL, resulted in a marked increase in TRAIL-induced apoptosis of T24 cells but showed no significant increase in toxicity to SV40 immortalized normal human uroepithelial cell-1. HDAC inhibition, especially with sodium butyrate and trichostatin A, led to increased TRAIL-R2 gene transcription that correlated with increased TRAIL-R2 surface expression. The increased TRAIL-R2 levels also resulted in accelerated death-inducing signaling complex (DISC) formation, caspase activation, and loss of mitochondrial membrane potential, which all contributed to the increase in tumor cell death. Collectively, these results show the therapeutic potential of combining HDAC inhibition with TRAIL as an alternative treatment for bladder cancer. (Cancer Res 2006; 66(1): 499-507)
Vascular Endothelial Growth Factor Receptor-1 Activation Mediates Epithelial to Mesenchymal Transition in Human Pancreatic Carcinoma Cells
Authors: Yang Anthony D. , Camp E. Ramsay , Fan Fan , Shen Lanlan , Gray Michael J. , Liu Wenbiao , Somcio Ray , Bauer Todd W. , Wu Yan , Hicklin Daniel J. , Ellis Lee M. 
Published: January 2006

Abstract
Our laboratory has shown that vascular endothelial growth factor receptor-1 (VEGFR-1) expression on human pancreatic cancer cell lines mediates cell migration and invasion. Because epithelial to mesenchymal transition (EMT) also plays a role in cell motility by altering the cell phenotype and morphology, we hypothesized that VEGFR-1 activation induces molecular alterations that mediate EMT. Our treatment of the human pancreatic cancer cell line L3.6pl with the VEGFR-1 ligands VEGF-A and VEGF-B led to morphologic changes characteristic of EMT, including loss of polarity, increased intercellular separation, and the presence of pseudopodia. Immunofluorescent staining with antibodies to E-cadherin and β-catenin showed that VEGFR-1 activation led to translocation of E-cadherin and β-catenin from their usual cell membrane–bound location to the cytoplasm and nucleus, respectively. Western blotting showed that VEGFR-1 activation led to decreased expression of the epithelial markers E-cadherin and plakoglobin, increased expression of the mesenchymal markers vimentin and N-cadherin, and increased nuclear expression of β-catenin. Pretreatment of tumor cells with a VEGFR-1 blocking antibody inhibited the VEGFR-1-induced immunohistochemical and molecular changes in E-cadherin. VEGFR-1 activation led to an increase in expression of the EMT-associated transcription factors Snail, Twist, and Slug. The changes mediated by VEGFR-1 in this pancreatic carcinoma cell line are highly consistent with the changes characteristic of EMT. Given our previous finding of VEGFR-1-mediated tumor cell invasion and migration in pancreatic carcinoma cells, we hypothesize that VEGFR-1 plays a role in tumor progression in pancreatic cancer through the induction of EMT. (Cancer Res 2006; 66(1): 46-51)
Cyclin B1 and Other Cyclins as Tumor Antigens in Immunosurveillance and Immunotherapy of Cancer
Authors: Egloff Ann Marie , Vella Laura A. , Finn Olivera J. 
Published: January 2006

Abstract
Uncontrolled cell division is an indispensable event in tumor progression, and numerous molecules involved in this process have been the focus of intense investigation in tumor biology. Cyclins, molecules that orchestrate normal cell cycle progression, are abnormally overexpressed in various human cancers. We review evidence that the immune system recognizes some abnormally expressed cyclins as tumor antigens, such as cyclin B1, and we analyze the potential of cyclins D, E, and A to serve a similar function in cancer immunosurveillance. (Cancer Res 2006; 66(1): 6-9)
Pancreatic Cancer in Mice and Man: The Penn Workshop 2004
Authors: Hruban Ralph H. , Rustgi Anil K. , Brentnall Teresa A. , Tempero Margaret A. , Wright Christopher V. , Tuveson David A. 
Published: January 2006

Abstract
A three-day conference cosponsored by the National Cancer Institute Mouse Models of Human Cancer Consortium and the Abramson Cancer Center of the University of Pennsylvania was convened on December 1, 2004, in Philadelphia, Pennsylvania. The purpose of the conference was to compare the histopathologic changes in murine models of exocrine pancreatic cancer to human disease and to discuss potential preclinical applications of these models. The participants of this international meeting included over 100 physicians and scientists with expertise in pancreatic cancer pathology, therapy, detection, and biology, and they were organized accordingly into working groups. The format of the meeting was a series of short presentations by individual participants followed by working group breakout sessions. The working groups presented their reports on the final day of the conference, and highlights of selected individual presentations and working group recommendations are summarized here and in an accompanying pathology consensus report. (Cancer Res 2006; 66(1): 14-7)
Eco‐efficiency and Its xsTerminology
Authors: Huppes Gjalt , Ishikawa Masanobu 
Published: January 2006

SummaryEco‐efficiency has been defined as a general goal of creating value while decreasing environmental impact. Leaving out the normative part of this concept, the empirical part refers to a ratio between environmental impact and economic cost or value. Two basic choices must be made in defining practical eco‐efficiency: which variable is in the denominator and which is in the numerator; and whether to specify environmental impact or improvement and value created or cost. Distinguishing between two situations, the general one of value creation and the specific one of environmental improvement efforts, and leaving the numerator‐denominator choice to the user, as diverging practices have developed, four basic types of ecoefficiency result: environmental intensity and environmental productivity in the realm of value creation; and environmental improvement cost and environmental cost‐effectiveness in the realm of environmental improvement measures.
The Sustainability Balanced Scorecard as a Framework for Eco‐efficiency Analysis
Authors: Möller Andreas , Schaltegger Stefan 
Published: January 2006

SummaryTo provide valuable support for successful decision‐making, managers need a balanced set of financial and nonfinancial measures that represent different requirements, strategic goals, strategies, resources, and capabilities and the causal relationships between these domains. The balanced scorecard is such a measurement system. As an open system the balanced scorecard facilitates the consideration of sustainability issues. But enhanced balanced scorecards require a new type of data. This is where eco‐efficiency analysis comes into play.This article discusses the relationship between so‐called sustainability balanced scorecards and eco‐efficiency analysis. Eco‐efficiency analysis not only provides a data source for sustainability balanced scorecards; in the perspective of environmental information systems it also serves as a link between the balanced scorecard and corporate environmental accounting systems so that eco‐efficiency as a component of an environmental information system becomes an adapter with two interfaces, which are characterized in this article. The main focus is on the principle of cause and effect, its different forms, and the implications for the design of appropriate information system components.