bluuebunny/crossref_metadata_2025_split huggingface dataset:
GSTM1 and GSTT1 Copy Number Variation in Population-based Studies of Endometrial Cancer Risk
Authors: Karageorgi Stalo , Prescott Jennifer , Wong Jason Y.Y. , Lee I-Min , Buring Julie E. , De Vivo Immaculata 
Published: July 2011

Abstract
Background: Glutathione S-transferases (GST) detoxify a broad range of carcinogenic metabolites and lack of GSTM1 and GSTT1 activity due to gene deletions are prevalent. The associations of GSTM1 and GSTT1 polymorphisms with endometrial cancer risk have been inconsistent.
Methods: We investigated gene dosage effects of GSTM1 and GSTT1 copy number in 441 endometrial cancer cases and 1,237 matched controls selected from the Nurses' Health Study and Women's Health Study, as well as gene–environment interactions.
Results: Carriers of at least 2 GSTT1 genes had an increased risk of endometrial cancer (OR = 1.51, 95% CI = 1.04–2.19; Ptrend = 0.04) compared with women who were GSTT1 null. GSTM1 was not associated with endometrial cancer risk (OR2/3 vs. 0 copies = 0.82, 95% CI = 0.52–1.27; Ptrend = 0.41). We did not observe effect modification of either the GSTM1 or GSTT1 association with cancer risk by smoking status, postmenopausal hormone use, or body mass index.
Conclusions: Our results suggested GSTM1 copy number does not influence endometrial cancer risk, whereas higher GSTT1 copy number may be associated with increased risk. Our findings supported that GSTT1 differs in its substrate specificity from GSTM1 and may generate intermediates more genotoxic to endometrial cells than the parent chemical. Future studies are needed to clarify this relationship.
Impact: We hypothesized risk associated with GST enzymes may differ depending on environmental and/or occupational exposures. Our assessment of gene–environment interactions suggested GSTM1 and GSTT1 are not involved in the in vivo human metabolism of estrogen and its metabolites. Cancer Epidemiol Biomarkers Prev; 20(7); 1447–52. ©2011 AACR.
A Long-term Prospective Study of Type-Specific Human Papillomavirus Infection and Risk of Cervical Neoplasia Among 20,000 Women in the Portland Kaiser Cohort Study
Authors: Schiffman Mark , Glass Andrew G. , Wentzensen Nicolas , Rush Brenda B. , Castle Philip E. , Scott David R. , Buckland Julie , Sherman Mark E. , Rydzak Greg , Kirk Peter , Lorincz Attila T. , Wacholder Sholom , Burk Robert D. 
Published: July 2011

Abstract
Background: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (≥CIN3). Adding HPV testing to cytology is recommended for women ≥30 but long-term prospective studies of HPV testing are rare.
Methods: Beginning in 1989–1990, ∼20,000 women in a prepaid health maintenance organization (median age = 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan–Meier estimates of cumulative probability for ≥CIN3, up to 18 years of follow-up.
Results: We observed 15 cases of invasive cervical cancer during the study period, and 189 cases of CIN3. Predictive values and Kaplan–Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against ≥CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8–15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2–6.6). The risk for ≥CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7).
Conclusion and Impact: The data from this cohort study show the long-term predictive value of HPV testing, particularly in women ≥30, and a possible role for distinguishing particularly carcinogenic types like HPV16. Cancer Epidemiol Biomarkers Prev; 20(7); 1398–409. ©2011 AACR.
The Efficacy of Computer-Delivered Treatment for Smoking Cessation
Authors: Reitzel Lorraine R. , McClure Jennifer B. , Cofta-Woerpel Ludmila , Mazas Carlos A. , Cao Yumei , Cinciripini Paul M. , Vidrine Jennifer Irvin , Li Yisheng , Wetter David W. 
Published: July 2011

Abstract
Background: The current study evaluated the efficacy of an individualized, hand-held computer-delivered treatment (CDT) versus standard treatment (ST) for the maintenance of smoking abstinence following a quit attempt.
Methods: Participants were 303 adult daily smokers randomized to CDT or ST, plus pharmacotherapy. Abstinence though 1 year was examined using logistic random intercept models, a type of generalized linear mixed model regression.
Results: Results did not support the efficacy of the CDT program through 1 year postquit in analyses adjusted for time and study site (OR = 0.84, 95% CI = 0.55–1.30), or after further adjusting for race/ethnicity, age, gender, education, marital status, and the number of cigarettes smoked per day before quitting (OR = 0.89, 95% CI = 0.57–1.39).
Conclusions: CDT did not increase short- or long-term abstinence rates over ST in this study.
Impact: Findings differ from some in the literature and suggest the need for continued research on the use of CDT for smoking cessation. Cancer Epidemiol Biomarkers Prev; 20(7); 1555–7. ©2011 AACR.
Menthol Should Not Be Given a Free Pass Based on Studies of Biomarkers of Toxicity
Authors: Clark Pamela I. , Gardiner Phillip 
Published: July 2011

Abstract
Exposure and toxicity studies comparing menthol and nonmenthol cigarettes have resulted in mixed results. On the basis of those results, cigarette manufacturers have concluded that there is no increased harm from the addition of menthol to cigarettes. We propose that such a narrow definition of harm is not appropriate in dealing with the issue of menthol, and its broader negative public health impact. Cancer Epidemiol Biomarkers Prev; 20(7); 1269–71. ©2011 AACR.
Human Polyomaviruses and Other Human Viruses in Neuroendocrine Tumors
Authors: Schmitt Markus , Höfler Daniela , Koleganova Nadezda , Pawlita Michael 
Published: July 2011

Abstract
Background: While the association of the Merkel cell polyomavirus (MCV) with the neuroendocrine Merkel cell carcinomas (MCC) has been shown recently, it is unknown whether other human polyomaviruses (HPyV) may be associated with neuroendocrine tumours (NETs) of distinct entities.
Methods: Using novel, highly sensitive polyomavirus genotyping assays, we evaluated the prevalence of eight distinct HPyVs in a selection of 51 NETs from different entities. In addition, we analyzed these NETs for the presence of DNA from 12 adeno-associated virus (AAV) genotypes, adeno virus-5, 27 mucosal human papillomavirus (HPV) genotypes, hepatitis B (HBV), 8 human herpes viruses (HHV), and xenotropic murine leukemia virus-related virus (XMRV).
Results: 43 of the 50 (86%) NETs were positive for the DNA integrity control. Of these, 2 of 3 MCCs (67%) were positive for MCV. NETs from other entities, however, were negative for all HPyVs. Only a small subset of lung and appendix NETs were positive for EBV, HHV-6, and -7.
Conclusion: While the association of MCV with MCC was confirmed, other human viruses could not be identified as potentially causative agents of other NETs.
Impact: Our findings suggest that the human viruses tested for in this study do not play a comparable role in NETs like the polyomavirus MCV in MCC. Cancer Epidemiol Biomarkers Prev; 20(7); 1558–61. ©2011 AACR.
Pre-experimental Familiarization Increases Hippocampal Activity for Both Targets and Lures in Recognition Memory: An fMRI Study
Authors: de Zubicaray Greig I. , McMahon Katie L. , Hayward Lydia , Dunn John C. 
Published: July 2011

Abstract
In the present study, items pre-exposed in a familiarization series were included in a list discrimination task to manipulate memory strength. At test, participants were required to discriminate strong targets and strong lures from weak targets and new lures. This resulted in a concordant pattern of increased “old” responses to strong targets and lures. Model estimates attributed this pattern to either equivalent increases in memory strength across the two types of items (unequal variance signal detection model) or equivalent increases in both familiarity and recollection (dual process signal detection [DPSD] model). Hippocampal activity associated with strong targets and lures showed equivalent increases compared with missed items. This remained the case when analyses were restricted to high-confidence responses considered by the DPSD model to reflect predominantly recollection. A similar pattern of activity was observed in parahippocampal cortex for high-confidence responses. The present results are incompatible with “noncriterial” or “false” recollection being reflected solely in inflated DPSD familiarity estimates and support a positive correlation between hippocampal activity and memory strength irrespective of the accuracy of list discrimination, consistent with the unequal variance signal detection model account.
A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells
Authors: Solito Samantha , Falisi Erika , Diaz-Montero Claudia Marcela , Doni Andrea , Pinton Laura , Rosato Antonio , Francescato Samuela , Basso Giuseppe , Zanovello Paola , Onicescu Georgiana , Garrett-Mayer Elizabeth , Montero Alberto J. , Bronte Vincenzo , Mandruzzato Susanna 
Published: July 2011

Abstract
We recently demonstrated that human BM cells can be treated in vitro with defined growth factors to induce the rapid generation of myeloid-derived suppressor cells (MDSCs), hereafter defined as BM-MDSCs. Indeed, combination of G-CSF + GM-CSF led to the development of a heterogeneous mixture of immature myeloid cells ranging from myeloblasts to band cells that were able to suppress alloantigen- and mitogen-stimulated T lymphocytes. Here, we further investigate the mechanism of suppression and define the cell subset that is fully responsible for BM-MDSC–mediated immune suppression. This population, which displays the structure and markers of promyelocytes, is however distinct from physiologic promyelocytes that, instead, are devoid of immuosuppressive function. In addition, we demonstrate that promyelocyte-like cells proliferate in the presence of activated lymphocytes and that, when these cells exert suppressive activity, they do not differentiate but rather maintain their immature phenotype. Finally, we show that promyelocyte-like BM-MDSCs are equivalent to MDSCs present in the blood of patients with breast cancer and patients with colorectal cancer and that increased circulating levels of these immunosuppressive myeloid cells correlate with worse prognosis and radiographic progression.
Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins
Authors: Ansar Sameer , Koska Juraj , Reaven Peter D 
Published: July 2011

Abstract
Cardiovascular disease (CVD) risk in type 2 diabetes (T2DM) is only partially reduced by intensive glycemic control. Diabetic dyslipidemia is suggested to be an additional important contributor to CVD risk in T2DM. Multiple lipid lowering medications effectively reduce fasting LDL cholesterol and triglycerides concentrations and several of them routinely reduce CVD risk. However, in contemporary Western societies the vasculature is commonly exposed to prolonged postprandial hyperlipidemia. Metabolism of these postprandial carbohydrates and lipids yields multiple proatherogenic products. Even a transient increase in these factors may worsen vascular function and induces impaired endothelial dependent vasodilatation, a predictor of atherosclerosis and future cardiovascular events. There is a recent increased appreciation for the role of gut-derived incretin hormones in controlling the postprandial metabolic milieu. Incretin-based medications have been developed and are now used to control postprandial hyperglycemia in T2DM. Recent data indicate that these medications may also have profound effects on postprandial lipid metabolism and may favorably influence several cardiovascular functions. This review discusses (1) the postprandial state with special emphasis on postprandial lipid metabolism and its role in endothelial dysfunction and cardiovascular risk, (2) the ability of incretins to modulate postprandial hyperlipidemia and (3) the potential of incretin-based therapeutic strategies to improve vascular function and reduce CVD risk.
Molecular and cellular correlates of the CIITA-mediated inhibition of HTLV-2 Tax-2 transactivator function resulting in loss of viral replication
Authors: Orlandi Chiara , Forlani Greta , Tosi Giovanna , Accolla Roberto S 
Published: July 2011

AbstractBackgroundMHC class II transactivator CIITA inhibits the function of HTLV-2 Tax-2 viral transactivator and, consequently, the replication of the virus in infected cells. Moreover overexpression of the nuclear factor NF-YB, that cooperates with CIITA for the expression of MHC class II genes, results also in inhibition of Tax-2 transactivation. The purpose of this investigation was to assess the cellular and molecular basis of the CIITA-mediated inhibition on Tax-2, and the relative role of NF-YB in this phenomenon.MethodsBy co-immunoprecipitation of lysates from 293T cells cotransfected with CIITA or fragments of it, and Tax-2 it was assessed whether the two factors interactin vivo. A similar approach was used to assess Tax-2-NF-YB interaction. In parallel, deletion fragments of CIITA were tested for the inhibition of Tax-2-dependent HTLV-2 LTR-luciferase transactivation. Subcellular localization of CIITA and Tax-2 was investigated by immunofluorescence and confocal microscopy.ResultsCIITA and Tax-2 interactin vivothrough at least two independent regions, at the 1-252 N-term and at the 410-1130 C-term, respectively. Interestingly only the 1-252 N-term region mediates Tax-2 functional inhibition. CIITA and Tax-2 are localized both in the cytoplasm and in the nucleus, when separately expressed. Instead, when coexpressed, most of Tax-2 colocalize with CIITA in cytoplasm and around the nuclear membrane. The Tax-2 minor remaining nuclear portion also co-localizes with CIITA. Interestingly, when CIITA nucleus-cytoplasm shuttling is blocked by leptomycin B treatment, most of the Tax-2 molecules are also blocked and co-localize with CIITA in the nucleus, suggesting that CIITA-Tax-2 binding does not preclude Tax-2 entry into the nucleus.Finally, the nuclear factor NF-YB, also strongly binds to Tax-2. Notably, although endogenous NF-YB does not inhibit Tax-2-dependent HTLV-2 LTR transactivation, it still binds to Tax-2, and in presence of CIITA, this binding seems to increase.ConclusionsThese results strongly suggest that CIITA inhibit Tax-2 by binding the viral transactivator both directly or through a tripartite interaction with NF-YB in. CIITA is therefore a viral restriction factor for HTLV-2 and this open the possibility to control HTLV-2 viral replication and spreading by the controlled induction of CIITA in infected cells
Meta-analysis of multiple microarray datasets reveals a common gene signature of metastasis in solid tumors
Authors: Daves Marla H , Hilsenbeck Susan G , Lau Ching C , Man Tsz-Kwong 
Published: July 2011

Abstract

Background
Metastasis is the number one cause of cancer deaths. Expression microarrays have been widely used to study metastasis in various types of cancer. We hypothesize that a meta-analysis of publicly available gene expression datasets in various tumor types can identify a signature of metastasis that is common to multiple tumor types. This common signature of metastasis may help us to understand the shared steps in the metastatic process and identify useful biomarkers that could predict metastatic risk.

Methods
We identified 18 publicly available gene expression datasets in the Oncomine database comparing distant metastases to primary tumors in various solid tumors which met our eligibility criteria. We performed a meta-analysis using a modified permutation counting method in order to obtain a common gene signature of metastasis. We then validated this signature in independent datasets using gene set expression comparison analysis with the LS-statistic.

Results
A common metastatic signature of 79 genes was identified in the metastatic lesions compared with primaries with a False Discovery Proportion of less than 0.1. Interestingly, all the genes in the signature, except one, were significantly down-regulated, suggesting that overcoming metastatic suppression may be a key feature common to all metastatic tumors. Pathway analysis of the significant genes showed that the genes were involved in known metastasis-associated pathways, such as integrin signaling, calcium signaling, and VEGF signaling. To validate the signature, we used an additional six expression datasets that were not used in the discovery study. Our results showed that the signature was significantly enriched in four validation sets with p-values less than 0.05.

Conclusions
We have modified a previously published meta-analysis method and identified a common metastatic signature by comparing primary tumors versus metastases in various tumor types. This approach, as well as the gene signature identified, provides important insights to the common metastatic process and a foundation for future discoveries that could have broad application, such as drug discovery, metastasis prediction, and mechanistic studies.
Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice
Authors: Akers Katherine G , Kushner Steven A , Leslie Ana T , Clarke Laura , van der Kooy Derek , Lerch Jason P , Frankland Paul W 
Published: July 2011

AbstractBackgroundChildren whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood.ResultsMice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing anin vitroneurosphere assay,in vivolabeling of new cells using BrdU, andin vivolabeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks.ConclusionsUsing a combination of techniques, including structural brain imaging,in vitroandin vivocell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.
The Protein Kinase A Pathway Regulates CYP17 Expression and Androgen Production in the Human Placenta
Authors: Escobar Julian C. , Carr Bruce R. 
Published: July 2011

Abstract

Background:
Our previous work demonstrated that the human placenta expresses CYP17 and is capable of de novo production of C-19 steroids; thus, it has intrinsic capacity to generate estrogens without fetal or maternal steroid precursors.

Objective:
Our objective was to elucidate the regulation of CYP17 expression and androgen production in the human trophoblasts.

Methods:
Fresh placentas and JEG-3 cells were used for all experiments. CYP17 mRNA analysis was performed via RT-PCR, and steroid products were quantified using RIA. To assess protein kinase A (PKA) pathway involvement, a pharmacological approach was used with forskolin (FSK) (10 μm), an activator, and H89 (10 μm), an inhibitor of the PKA pathway.

Results:
FSK treatment amplified CYP17 mRNA levels in both cell types when compared with basal, with levels increasing over time, peaking at 72 h, and appearing more robust in primary cells; this difference ranged from 2- to 10-fold and was statistically significant at all time points. Meanwhile, H89 reduced CYP17 levels and blunted the effect of FSK when the treatments were combined. Similarly, FSK treatment significantly increased 17α-hydroxyprogesterone concentration in both cell cultures, and H89 blunted that effect as well.

Conclusions:
We confirm again that the human trophoblast expresses CYP17 and is able to generate estrogen precursors. We demonstrate that this process is regulated, at least in part, by the cAMP/PKA pathway.
Differential Nongenetic Impact of Birth Weight Versus Third-Trimester Growth Velocity on Glucose Metabolism and Magnetic Resonance Imaging Abdominal Obesity in Young Healthy Twins
Authors: Pilgaard Kasper , Hammershaimb Mosbech Thomas , Grunnet Louise , Eiberg Hans , Van Hall Gerrit , Fallentin Eva , Larsen Torben , Larsen Rasmus , Poulsen Pernille , Vaag Allan 
Published: July 2011

Abstract

Context:
Low birth weight is associated with type 2 diabetes, which to some extent may be mediated via abdominal adiposity and insulin resistance. Fetal growth velocity is high during the third trimester, constituting a potential critical window for organ programming. Intra-pair differences among monozygotic twins are instrumental in determining nongenetic associations between early environment and adult metabolic phenotype.

Objective:
Our objective was to investigate the relationship between size at birth and third-trimester growth velocity on adult body composition and glucose metabolism using intra-pair differences in young healthy twins.

Methods:
Fifty-eight healthy twins (42 monozygotic/16 dizygotic) aged 18–24 yr participated. Insulin sensitivity was assessed using hyperinsulinemic-euglycemic clamps. Whole-body fat was assessed by dual-energy x-ray absorptiometry scan, whereas abdominal visceral and sc fat (L1–L4) were assessed by magnetic resonance imaging. Third-trimester growth velocity was determined by repeated ultrasound examinations.

Results:
Size at birth was nongenetically inversely associated with adult visceral and sc fat accumulation but unrelated to adult insulin action. In contrast, fetal growth velocity during third trimester was not associated with adult visceral or sc fat accumulation. Interestingly, third-trimester growth was associated with insulin action in a paradoxical inverse manner.

Conclusions:
Abdominal adiposity including accumulation of both sc and visceral fat may constitute primary nongenetic factors associated with low birth weight and reduced fetal growth before the third trimester. Reduced fetal growth during vs. before the third trimester may define distinct adult trajectories of metabolic and anthropometric characteristics influencing risk of developing type 2 diabetes.