bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen-Dependent and Estrogen-Independent Mechanisms Contribute to AIB1-Mediated Tumor Formation
Authors: Torres-Arzayus Maria I. , Zhao Jin , Bronson Roderick , Brown Myles 
Published: May 2010

Abstract
We have previously reported the oncogenic properties of the gene amplified in breast cancer 1 (AIB1), a member of the p160 family of hormone receptor coactivators. In a transgenic mouse model, AIB1 overexpression resulted in a high incidence of tumors in various tissues, including mammary gland, uterus, lung, and pituitary. To determine whether the AIB1 oncogenicity in this model depended on its function as an estrogen receptor (ER) coactivator, we abolished ER signaling through two independent approaches, by performing ovariectomy on AIB1 transgenic (AIB1-tg) mice to prevent gonadal estrogen production and by crossing AIB1-tg mice with ERα-null mutant mice. Ovariectomized (ovx) mice, but not AIB1 × ERα−/− mice, still developed mammary gland hyperplasia and ductal carcinoma in situ. Both approaches, however, completely prevented the development of invasive mammary tumors, indicating that invasive mammary tumor formation is strictly estrogen dependent. Once developed, AIB1-induced mammary tumors can subsequently lose their dependence on estrogen: Injection of ERα(+) tumor cell lines derived from such tumors into ovx or untreated wild-type mice resulted in a similar rate of tumor growth in both groups. Surprisingly, however, ovx mice had an ∼4-fold higher rate of metastasis formation, suggesting that estrogen provided some protection from metastasis formation. Lastly, our experiments identified oncogenic functions of AIB1 that are independent of its ER coactivation, as both approaches, ovariectomy and ER−/− crosses, still resulted in a high incidence of tumors in the lung and pituitary. We therefore conclude that AIB1 can exert its oncogenicity through tissue-specific estrogen-dependent and estrogen-independent functions. Cancer Res; 70(10); 4102–11. ©2010 AACR.
Preclinical Evaluation of an 131I-Labeled Benzamide for Targeted Radiotherapy of Metastatic Melanoma
Authors: Joyal John L. , Barrett John A. , Marquis John C. , Chen Jianqing , Hillier Shawn M. , Maresca Kevin P. , Boyd Marie , Gage Kenneth , Nimmagadda Sridhar , Kronauge James F. , Friebe Matthias , Dinkelborg Ludger , Stubbs James B. , Stabin Michael G. , Mairs Rob , Pomper Martin G. , Babich John W. 
Published: May 2010

Abstract
Radiolabeled benzamides are attractive candidates for targeted radiotherapy of metastatic melanoma as they bind melanin and exhibit high tumor uptake and retention. One such benzamide, N-(2-diethylamino-ethyl)-4-(4-fluoro-benzamido)-5-iodo-2-methoxy-benzamide (MIP-1145), was evaluated for its ability to distinguish melanin-expressing from amelanotic human melanoma cells, and to specifically localize to melanin-containing tumor xenografts. The binding of [131I]MIP-1145 to melanoma cells in vitro was melanin dependent, increased over time, and insensitive to mild acid treatment, indicating that it was retained within cells. Cold carrier MIP-1145 did not reduce the binding, consistent with the high capacity of melanin binding of benzamides. In human melanoma xenografts, [131I]MIP-1145 exhibited diffuse tissue distribution and washout from all tissues except melanin-expressing tumors. Tumor uptake of 8.82% injected dose per gram (ID/g) was seen at 4 hours postinjection and remained at 5.91% ID/g at 24 hours, with tumor/blood ratios of 25.2 and 197, respectively. Single photon emission computed tomography imaging was consistent with tissue distribution results. The administration of [131I]MIP-1145 at 25 MBq or 2.5 GBq/m2 in single or multiple doses significantly reduced SK-MEL-3 tumor growth, with multiple doses resulting in tumor regression and a durable response for over 125 days. To estimate human dosimetry, gamma camera imaging and pharmacokinetic analysis was performed in cynomolgus monkeys. The melanin-specific binding of [131I]MIP-1145 combined with prolonged tumor retention, the ability to significantly inhibit tumor growth, and acceptable projected human dosimetry suggest that it may be effective as a radiotherapeutic pharmaceutical for treating patients with metastatic malignant melanoma. Cancer Res; 70(10); 4045–53. ©2010 AACR.
Microtubule Dynamics, Mitotic Arrest, and Apoptosis: Drug-Induced Differential Effects of βIII-Tubulin
Authors: Gan Pei Pei , McCarroll Joshua A. , Po'uha Sela T. , Kamath Kathy , Jordan Mary Ann , Kavallaris Maria 
Published: May 2010

Abstract
Overexpression of βIII-tubulin is associated with resistance to tubulin-binding agents (TBA) in a range of tumor types. We previously showed that small interfering RNA silencing of βIII-tubulin expression hypersensitized non–small cell lung cancer cells to TBAs. To determine whether βIII-tubulin mediates its effect on drug-induced mitotic arrest and cell death by differentially regulating microtubule behavior, the effects of βIII-tubulin knockdown on microtubule dynamics were analyzed in H460 non–small cell lung cancer cells stably expressing green fluorescent protein-βI-tubulin. Interphase cells were examined at three vincristine and paclitaxel concentrations that (a) inhibited cell proliferation, (b) induced 5% to 10% mitotic arrest, and (c) induced 30% to 40% mitotic arrest. In the absence of either drug, βIII-tubulin knockdown caused no significant change in microtubule dynamic instability. At 2 nmol/L vincristine (IC50), overall microtubule dynamicity was significantly suppressed in βIII-tubulin knockdowns (−31.2%) compared with controls (−6.5%). Similar results were obtained with paclitaxel, suggesting that knockdown of βIII-tubulin induces hypersensitivity by enhancing stabilization of microtubule dynamics at low drug concentrations. At higher drug concentrations (≥40 nmol/L vincristine; ≥20 nmol/L paclitaxel), βIII-tubulin knockdown resulted in significantly reduced suppressive effects on microtubule dynamicity with little or no further increase in mitotic arrest, compared with control cells. Importantly, apoptosis was markedly increased by βIII-tubulin knockdown independent of further suppression of microtubule dynamics and mitotic arrest. These results show that βIII-tubulin knockdown enhances the effectiveness of TBAs through two mechanisms: suppression of microtubule dynamics at low drug concentrations and a mitosis-independent mechanism of cell death at higher drug concentrations. Mol Cancer Ther; 9(5); 1339–48. ©2010 AACR.
17-Allylamino-17-Demethoxygeldanamycin and MEK1/2 Inhibitors Kill GI Tumor Cells via Ca2+-Dependent Suppression of GRP78/BiP and Induction of Ceramide and Reactive Oxygen Species
Authors: Walker Teneille , Mitchell Clint , Park Margaret A. , Yacoub Adly , Rahmani Mohamed , Häussinger Dieter , Reinehr Roland , Voelkel-Johnson Christina , Fisher Paul B. , Grant Steven , Dent Paul 
Published: May 2010

Abstract
The present studies determine in greater detail the molecular mechanisms upstream of the CD95 death receptor by which geldanamycin heat shock protein 90 inhibitors and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) inhibitors interact to kill carcinoma cells. MEK1/2 inhibition enhanced 17-allylamino-17-demethoxygeldanamycin (17AAG) toxicity that was suppressed in cells deleted for mutant active RAS that were nontumorigenic but was magnified in isogenic tumorigenic cells expressing Harvey RAS V12 or Kirsten RAS D13. MEK1/2 inhibitor and 17AAG treatment increased intracellular Ca2+ levels and reduced GRP78/BiP expression in a Ca2+-dependent manner. GRP78/BiP overexpression, however, also suppressed drug-induced intracellular Ca2+ levels. MEK1/2 inhibitor and 17AAG treatment increased reactive oxygen species (ROS) levels that were blocked by quenching Ca2+ or overexpression of GRP78/BiP. MEK1/2 inhibitor and 17AAG treatment activated CD95 and inhibition of ceramide synthesis; ROS or Ca2+ quenching blocked CD95 activation. In SW620 cells that are patient matched to SW480 cells, MEK1/2 inhibitor and 17AAG toxicity was significantly reduced, which correlated with a lack of CD95 activation and lower expression of ceramide synthase 6 (LASS6). Overexpression of LASS6 in SW620 cells enhanced drug-induced CD95 activation and enhanced tumor cell killing. Inhibition of ceramide signaling abolished drug-induced ROS generation but not drug-induced cytosolic Ca2+ levels. Thus, treatment of tumor cells with MEK1/2 inhibitor and 17AAG induces cytosolic Ca2+ and loss of GRP78/BiP function, leading to de novo ceramide synthesis pathway activation that plays a key role in ROS generation and CD95 activation. Mol Cancer Ther; 9(5); 1378–95. ©2010 AACR.
Comparison of the Long-Term Safety and Efficacy of Drug-Eluting and Bare-Metal Stent Implantation in Saphenous Vein Grafts
Authors: Latib Azeem , Ferri Luca , Ielasi Alfonso , Cosgrave John , Godino Cosmo , Bonizzoni Erminio , Romagnoli Enrico , Chieffo Alaide , Valgimigli Marco , Penzo Carlo , Carlino Mauro , Michev Iassen , Sangiorgi Giuseppe M. , Montorfano Matteo , Airoldi Flavio , Colombo Antonio 
Published: May 2010

Background—
Concerns about the long-term safety of drug-eluting stents (DES) in saphenous vein grafts has become an area of controversy and uncertainty.

Methods and Results—

In this retrospective registry, we compared the outcomes in 127 patients (143 lesions) treated with DES from April 2002 to June 2006 (DES group) with 131 patients (160 lesions) treated with bare-metal stents in the preceding 36 months (bare-metal stent group). End points analyzed were cumulative death, myocardial infarction, and target vessel revascularization at 2 years after stent implantation. The DES group was significantly (
P
<0.05) more complex with a greater frequency of diabetes (33.1%versus 15.3%), older grafts (11.6±5.3 years versus 9.6±5.2 years), restenotic lesions (23.8% versus 4.4%), total occlusions (7.7% versus 1.2%), and smaller grafts (3.16±0.66 mm versus 3.44±0.76 mm) treated with longer stents (34.1±25.1 mm versus 22.7±11.6 mm). At 2 years, there was no statistical difference in death (8.7% versus 7.8%), myocardial infarction (6.3% versus 9.4%), or target vessel revascularization (19.7% versus 24.2%) between DES and bare-metal stents, respectively. A propensity analysis to adjust for baseline differences suggested that there was no observed association between DES and increased mortality (hazard ratio, 0.72; 95% CI, 0.21 to 2.44;
P
=0.60) but possibly an association with a reduction in target vessel revascularization (hazard ratio, 0.31; 95% CI, 0.14 to 0.66;
P
=0.002).

Conclusions—
Despite being implanted in patients and lesions more complex than the bare-metal stent group, there was no observed association between DES implantation in saphenous vein grafts and an increase in late mortality. DES may maintain their efficacy in reducing revascularization rates in diseased saphenous vein grafts over a 2-year follow-up period.
The feasibility of assessing alcohol use among college students using wireless mobile devices: Implications for health education and behavioural research
Authors: Mays Darren , Cremeens Jennifer , Usdan Stuart , Martin Ryan J , Arriola Kimberly J , Bernhardt Jay M 
Published: May 2010

Objective: This study examined the feasibility of using wireless mobile devices (MDs) to collect daily alcohol information among college students, in particular examining feasibility in the context of costs associated with the use of wireless MDs. This study reports on practical aspects of using MDs to collect alcohol data, including compliance, technical success, user preferences for completing MD-based assessments, and cost. Setting: The study took place at a large, public university in the south-eastern United States. Design: A two-group, randomized design was used. A daily assessment of alcohol use administered using wireless MDs was completed by a group of college students ( n=86) for 30 days and compared to a paper-based (PB) daily assessment of alcohol use completed by a second group of college students ( n=83) over the same time period. Results: Completion rates for the MD assessment (85.8 per cent) were comparable to the PB assessment (97.6 per cent) given the differences in mode of administration. Participants found the MDs easy to use (83.7 per cent), easy to read (94.2 per cent), and on average liked completing the daily MD assessment ( M 4.47, SD 1.16) significantly more than respondents liked completing the PB assessment ( M 3.88, SD 1.08; t [164] 3.84, p < 0.001). Few participants in the MD group reported that they were uncomfortable (9.3 per cent) or nervous (2.3 per cent) completing daily assessments using the MDs. Conclusion: Results indicate that the feasibility of using MDs for data collection may be influenced by user preferences and should be tested on different health behaviours in more diverse populations.
Randomized controlled trial to increase physical activity among insufficiently active women following their participation in a mass event
Authors: Lane Aoife , Murphy Niamh , Bauman Adrian , Chey Tien 
Published: May 2010

Objective: To assess the impact of a community based, low-contact intervention on the physical activity habits of insufficiently active women. Design: Randomized controlled trial. Participants: Inactive Irish women. Method: A population sample of women participating in a mass 10 km event were up followed at 2 and 6 months, and those who had relapsed to insufficient levels of physical activity were recruited to this trial and randomly allocated to an intervention or control group. A tailored physical activity booklet was mailed to participants in the intervention group; a placebo booklet was administered to the control group. Three weeks after the dissemination of materials, members of the intervention group were contacted by phone to check the receipt and use of the booklets. Six weeks post baseline, questionnaires were administered to all participants. Results: Receipt and use of materials and an increase in self-efficacy was significantly greater in the intervention group. Mean total physical activity increased significantly between baseline and follow-up in both the intervention (+ 109 min) and control groups (+ 139 min), with increases most apparent among the least active participants of both groups. There was also a significant increase in the number of respondents meeting minimum physical activity guidelines at follow-up. Conclusion: There was no difference in the increases in physical activity, which were greatest among least active participants, between intervention and control groups, suggesting that the tailored materials used in this trial did not have a greater impact than standard health information and contact alone.
Adolescents’ preferences regarding sex education and relationship education
Authors: Turnbull Triece , van Schaik Paul , van Wersch Anna 
Published: May 2010

Objective: The aim of the current study was to examine adolescents’ perceptions of the quality of a Sex and Relationship Education (SRE) intervention, their preferences for sources of SRE and how these vary as a function of gender, school’s faith and school type. Design: A non-experimental design was used. Setting: The participants ( N = 759 adolescent girls [ n = 448] and boys [ n = 326]), who had attended an SRE intervention and had previously been given formal SRE within the school they attended, completed a survey questionnaire. Method: A questionnaire was designed to assess perceptions and preference of the intervention. The data were analysed using logistic regression. Results: Adolescents judged the sex education intervention to be of high quality and enjoyed being taught by sexual-health workers. Preferred sources of SRE included sexual-health workers, parents and peers as well as the media. Gender, school’s faith (Church of England or Catholic) and school type (mainstream, special needs) were predictors of preference for various aspects of SRE. Conclusion: The results highlight the crucial role of experienced qualified SRE educators, but also the supplementary role of parents and peers as well as the auxiliary role of Internet sites, magazines, phone lines and schools. Stereotypical preferences of boys and girls outside SRE seem to be perpetuated in SRE, and special needs and mainstream adolescents’ preferences are consistent with their communication and education outside SRE.
Quantitative Magnetic Resonance Imaging Detects Changes in Meniscal Volume In Vivo After Partial Meniscectomy
Authors: Bowers Megan E. , Tung Glenn A. , Oksendahl Heidi L. , Hulstyn Michael J. , Fadale Paul D. , Machan Jason T. , Fleming Braden C. 
Published: May 2010

Background: Quantifying changes in meniscal volume in vivo before and after partial meniscectomy (PM) could help elucidate the mechanisms involved in osteoarthritis development after meniscal injury and its surgical treatment. Purpose/Hypothesis: To determine whether quantitative magnetic resonance imaging (qMRI) can detect the immediate reduction in meniscal volume created by PM, while ruling out changes in unresected structures. We hypothesized that qMRI would be reliable for determining meniscal volume within the repeated images of unresected menisci. Additionally, we expected no significant difference in volume between the uninjured menisci of the injured knees and the same menisci of the uninjured knees. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Ten subjects with meniscal tears were evaluated with 3-T MRI before and after arthroscopic PM. Manual segmentation was used to create models of the menisci and to determine the preoperative and postoperative meniscal volumes for each subject. The responsiveness and reliability of qMRI for determining meniscal volume in vivo were evaluated using these measurements. We expected a decrease in volume of the resected menisci, but not in the uninjured menisci, after surgery. Results: The mean preoperative volume of the injured menisci was significantly greater than the mean postoperative volume (2896 ± 277 vs 2480 ± 277 mm3; P = .000). There was no significant difference between the mean preoperative and postoperative volumes of the uninjured menisci (2687 ± 256 vs 2694 ± 256 mm3; P = 1.000). Conclusion: Manual segmentation demonstrated a significant reduction in the volume of the surgically resected menisci after PM, but no significant change in the volume of unresected meniscal tissue, indicating that the manual segmentation method is responsive. Clinical Relevance: This approach offers a novel, reliable method to study the relationship between the volume of meniscal tissue removed during PM and subsequent patient outcomes during long-term clinical studies.
Endothelial protein C receptor–expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver
Authors: Iwasaki Hiroko , Arai Fumio , Kubota Yoshiaki , Dahl Maria , Suda Toshio 
Published: May 2010

AbstractHematopoietic stem cells (HSCs) are maintained in specialized niches in adult bone marrow. However, niche and HSC maintenance mechanism in fetal liver (FL) still remains unclear. Here, we investigated the niche and the molecular mechanism of HSC maintenance in mouse FL using HSCs expressing endothelial protein C receptor (EPCR). The antiapoptotic effect of activated protein C (APC) on EPCR+ HSCs and the expression of protease-activated receptor 1 (Par-1) mRNA in these cells suggested the involvement of the cytoprotective APC/EPCR/Par-1 pathway in HSC maintenance. Immunohistochemistry revealed that EPCR+ cells were localized adjacent to, or integrated in, the Lyve-1+ sinusoidal network, where APC and extracellular matrix (ECM) are abundant, suggesting that HSCs in FL were maintained in the APC- and ECM-rich perisinusoidal niche. EPCR+ HSCs were in a relatively slow cycling state, consistent with their high expression levels of p57 and p18. Furthermore, the long-term reconstitution activity of EPCR+ HSCs decreased significantly after short culture but not when cocultured with feeder layer of FL-derived Lyve-1+ cells, which suggests that the maintenance of the self-renewal activity of FL HSCs largely depended on the interaction with the perisinusoidal niche. In conclusion, EPCR+ HSCs resided in the perisinusoidal niche in mouse FL.
Influence of bone marrow stromal microenvironment on forodesine-induced responses in CLL primary cells
Authors: Balakrishnan Kumudha , Burger Jan A. , Quiroga Maite P. , Henneberg Marina , Ayres Mary L. , Wierda William G. , Gandhi Varsha 
Published: May 2010

AbstractForodesine, a purine nucleoside phosphorylase inhibitor, displays in vitro activity in chronic lymphocytic leukemia (CLL) cells in presence of dGuo, which is the basis for an ongoing clinical trial in patients with fludarabine-refractory CLL. Initial clinical data indicate forodesine has significant activity on circulating CLL cells, but less activity in clearing CLL cells from tissues such as marrow. In tissue microenvironments, lymphocytes interact with accessory stromal cells that provide survival and drug-resistance signals, which may account for residual disease. Therefore, we investigated the impact of marrow stromal cells (MSCs) on forodesine-induced response in CLL lymphocytes. We demonstrate that spontaneous and forodesine-induced apoptosis of CLL cells was significantly inhibited by human and murine MSCs. Forodesine-promoted dGuo triphosphate (dGTP) accumulation and GTP and ATP depletion in CLL cells was inhibited by MSCs, providing a mechanism for resistance. Also, MSCs rescued CLL cells from forodesine-induced RNA- and protein-synthesis inhibition and stabilized and increased Mcl-1 transcript and protein levels. Conversely, MSC viability was not affected by forodesine and dGuo. Collectively, MSC-induced biochemical changes antagonized forodesine-induced CLL cell apoptosis. This provides a biochemical mechanism for MSC-derived resistance to forodesine and emphasizes the need to move toward combinations with agents that interfere with the microenvironment's protective role for improving current therapeutic efforts.
Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals
Authors: Quesada Víctor , Velasco Gloria , Puente Xose S , Warren Wesley C , López-Otín Carlos 
Published: May 2010

Abstract

Background
The degradome -the complete repertoire of proteases in an organism- is involved in multiple key biological and pathological processes. Previous studies in several organisms have yielded sets of curated protease sequences which may be used to characterize the degradome in a novel genome by similarity. Differences between degradomes can then be related to physiological traits of the species under study. Therefore, the sequencing of the zebra finch genome allows the comparison between the degradomes of mammals and birds and may help to understand the biological peculiarities of the zebra finch.

Results
A set of curated protease sequences from humans and chicken was used to predict the sequences of 460 protease and protease-like genes in the zebra finch genome. This analysis revealed important differences in the evolution of mammalian and bird degradomes, including genomic expansions and deletions of caspases, cytotoxic proteases, kallikreins, matrix metalloproteases, and trypsin-like proteases. Furthermore, we found several zebra finch-specific features, such as duplications in CASP3 and BACE, and a large genomic expansion of acrosin.

Conclusions
We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms. Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions.