bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells
Authors: Shahjee Hanief M , Koch Kristopher R , Guo Li , Zhang Chen-Ou , Keay Susan K 
Published: January 2011

Abstract

Background
Urinary bladder cancer is a common malignancy worldwide, and outcomes for patients with advanced bladder cancer remain poor. Antiproliferative factor (APF) is a potent glycopeptide inhibitor of epithelial cell proliferation that was discovered in the urine of patients with interstitial cystitis, a disorder with bladder epithelial thinning and ulceration. APF mediates its antiproliferative activity in primary normal bladder epithelial cells via cytoskeletal associated protein 4 (CKAP4). Because synthetic asialo-APF (as-APF) has also been shown to inhibit T24 bladder cancer cell proliferation at nanomolar concentrations in vitro, and because the peptide segment of APF is 100% homologous to part of frizzled 8, we determined whether CKAP4 mediates as-APF inhibition of proliferation and/or downstream Wnt/frizzled signaling events in T24 cells.

Methods
T24 cells were transfected with double-stranded siRNAs against CKAP4 and treated with synthetic as-APF or inactive control peptide; cells that did not undergo electroporation and cells transfected with non-target (scrambled) double-stranded siRNA served as negative controls. Cell proliferation was determined by 3H-thymidine incorporation. Expression of Akt, glycogen synthase kinase 3β (GSK3β), β-catenin, p53, and matrix metalloproteinase 2 (MMP2) mRNA was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Akt, GSK-3β, MMP2, β-catenin, and p53 protein expression, plus Akt, GSK-3β, and β-catenin phosphorylation, were determined by Western blot.

Results
T24 cell proliferation, MMP2 expression, Akt ser473 and thr308 phosphorylation, GSK3β tyr216 phosphorylation, and β-catenin ser45/thr41 phosphorylation were all decreased by APF, whereas p53 expression, and β-catenin ser33,37/thr41 phosphorylation, were increased by APF treatment in non-electroporated and non-target siRNA-transfected cells. Neither mRNA nor total protein expression of Akt, GSK3β, or β-catenin changed in response to APF in these cells. In addition, the changes in cell proliferation, MMP2/p53 mRNA and protein expression, and Akt/GSK3β/β-catenin phosphorylation in response to APF treatment were all specifically abrogated following CKAP4 siRNA knockdown.

Conclusions
Synthetic as-APF inhibits cell proliferation in T24 bladder carcinoma cells via the CKAP4 receptor. The mechanism for this inhibition involves regulating phosphorylation of specific cell signaling molecules (Akt, GSK3β, and β-catenin) plus mRNA and protein expression of p53 and MMP2.
MicroRNAs involved in neoplastic transformation of liver cancer stem cells
Authors: Li Ren , Qian Niansong , Tao Kaishan , You Nan , Wang Xinchuan , Dou Kefeng 
Published: January 2011

Abstract

Background
The existence of cancer stem cells in hepatocellular carcinoma (HCC) has been verified by characterizing side population (SP) cells based on efflux of Hoechst 33342 dye from stem cells. Recent advances in microRNA (miRNA) biology have revealed that miRNAs play an important role in embryonic development and tumorigenesis. However, it is still unclear which miRNAs participate in the neoplastic transformation of liver cancer stem cells (LCSCs) during hepatocarcinogenesis.

Methods
To identify the unique set of miRNAs differentially regulated in LCSCs, we applied SP sorting to primary cultures of F344 rat HCC cancer cells treated with diethylnitrosamine (DEN) and normal syngenic fetal liver cells, and the stem-like characteristics of SP cells were verified through detecting expression of CD90.1, AFP and CK-7. Global miRNA expression profiles of two groups of SP cells were screened through microarray platform.

Results
A total of 68 miRNAs, including miR-10b, miR-21, miR-470*, miR-34c-3p, and let-7i*, were identified as overexpressed in SP of HCC cells compared to fetal liver cells. Ten miRNAs were underexpressed, including miR-200a* and miR-148b*. These miRNAs were validated using stem-loop real-time reverse transcriptase polymerase chain reaction (RT-PCR).

Conclusions
Our results suggest that LCSCs may have a distinct miRNA expression fingerprint during hepatocarcinogenesis. Dissecting these relationships will provide a new understanding of the function of miRNA in the process of neoplastic transformation of LCSCs.
Microarray-based analysis of microRNA expression in breast cancer stem cells
Authors: Sun Jian-guo , Liao Rong-xia , Qiu Jun , Jin Jun-yu , Wang Xin-xin , Duan Yu-zhong , Chen Fang-lin , Hao Ping , Xie Qi-chao , Wang Zhi-xin , Li De-zhi , Chen Zheng-tang , Zhang Shao-xiang 
Published: January 2011

Abstract

Background
This study aimed to determine the miRNA profile in breast cancer stem cells (BCSCs) and to explore the functions of characteristic BCSC miRNAs.

Methods
We isolated ESA+CD44+CD24-/low BCSCs from MCF-7 cells using fluorescence-activated cell sorting (FACS). A human breast cancer xenograft assay was performed to validate the stem cell properties of the isolated cells, and microarray analysis was performed to screen for BCSC-related miRNAs. These BCSC-related miRNAs were selected for bioinformatic analysis and target prediction using online software programs.

Results
The ESA+CD44+CD24-/low cells had up to 100- to 1000-fold greater tumor-initiating capability than the MCF-7 cells. Tumors initiated from the ESA+CD44+CD24-/low cells were included of luminal epithelial and myoepithelial cells, indicating stem cell properties. We also obtained miRNA profiles of ESA+CD44+CD24-/low BCSCs. Most of the possible targets of potential tumorigenesis-related miRNAs were oncogenes, anti-oncogenes or regulatory genes.

Conclusions
We identified a subset of miRNAs that were differentially expressed in BCSCs, providing a starting point to explore the functions of these miRNAs. Evaluating characteristic BCSC miRNAs represents a new method for studying breast cancer-initiating cells and developing therapeutic strategies aimed at eradicating the tumorigenic subpopulation of cells in breast cancer.
The reliability of toe systolic pressure and the toe brachial index in patients with diabetes
Authors: Romanos Mary T , Raspovic Anita , Perrin Byron M 
Published: January 2011

AbstractBackgroundThe Ankle Brachial Index is a useful clinical test for establishing blood supply to the foot. However, there are limitations to this method when conducted on people with diabetes. As an alternative to the Ankle Brachial Index, measuring Toe Systolic Pressures and the Toe Brachial Index have been recommended to assess the arterial blood supply to the foot. This study aimed to determine the intra and inter‐rater reliability of the measurement of Toe Systolic Pressure and the Toe Brachial Index in patients with diabetes using a manual measurement system.MethodsThis was a repeated measures, reliability study. Three raters measured Toe Systolic Pressure and the Toe Brachial Index in thirty participants with diabetes. Measurement sessions occurred on two occasions, one week apart, using a manual photoplethysmography unit (Hadeco Smartdop 45) and a standardised measurement protocol.ResultsThe mean intra‐class correlation for intra‐rater reliability for toe systolic pressures was 0.87 (95% LOA: ‐25.97 to 26.06 mmHg) and the mean intra‐class correlation for Toe Brachial Indices was 0.75 (95% LOA: ‐0.22 to 0.28). The intra‐class correlation for inter‐rater reliability was 0.88 for toe systolic pressures (95% LOA: ‐22.91 to 29.17.mmHg) and 0.77 for Toe Brachial Indices (95% LOA: ‐0.21 to 0.22).ConclusionDespite the reasonable intra‐class correlation results, the range of error (95% LOA) was broad. This raises questions regarding the reliability of using a manual sphygmomanometer and PPG for the Toe Systolic Pressure and Toe Brachial Indice.
Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and serous ovarian tumors
Authors: Penumatsa Krishna , Edassery Seby L , Barua Animesh , Bradaric Michael J , Luborsky Judith L 
Published: January 2011

Abstract

Background
We showed there are specific ALDH1 autoantibodies in ovarian autoimmune disease and ovarian cancer, suggesting a role for ALDH1 in ovarian pathology. However, there is little information on the ovarian expression of ALDH1. Therefore, we compared ALDH1 expression in normal ovary and benign and malignant ovarian tumors to determine if ALDH1 expression is altered in ovarian cancer. Since there is also recent interest in ALDH1 as a cancer stem cell (CSC) marker, we assessed co-expression of ALDH1 with CSC markers in order to determine if ALDH1 is a potential CSC marker in ovarian cancer.

Methods
mRNA and protein expression were compared in normal human ovary and serous ovarian tumors using quantitative Reverse-Transcriptase PCR, Western blot (WB) and semi-quantitative immunohistochemistry (IHC). ALDH1 enzyme activity was confirmed in primary ovarian cells by flow cytometry (FC) using ALDEFLUOR assay.

Results
ALDH1 mRNA expression was significantly reduced (p < 0.01; n = 5) in malignant tumors compared to normal ovaries and benign tumors. The proportion of ALDH1+ cells was significantly lower in malignant tumors (17.1 ± 7.61%; n = 5) compared to normal ovaries (37.4 ± 5.4%; p < 0.01; n = 5) and benign tumors (31.03 ± 6.68%; p < 0.05; n = 5). ALDH1+ cells occurred in the stroma and surface epithelium in normal ovary and benign tumors, although surface epithelial expression varied more in benign tumors. Localization of ALDH1 was heterogeneous in malignant tumor cells and little ALDH1 expression occurred in poorly differentiated malignant tumors. In benign tumors the distribution of ALDH1 had features of both normal ovary and malignant tumors. ALDH1 protein expression assessed by IHC, WB and FC was positively correlated (p < 0.01). ALDH1 did not appear to be co-expressed with the CSC markers CD44, CD117 and CD133 by IHC.

Conclusions
Total ALDH1 expression is significantly reduced in malignant ovarian tumors while it is relatively unchanged in benign tumors compared to normal ovary. Thus, ALDH1 expression in the ovary does not appear to be similar to breast, lung or colon cancer suggesting possible functional differences in these cancers.

Significance
These observations suggest that reduced ALDH1 expression is associated with malignant transformation in ovarian cancer and provides a basis for further study of the mechanism of ALDH1 in this process.
Attitudes to routine HIV counselling and testing, and knowledge about prevention of mother to child transmission of HIV in eastern Uganda: a cross‐sectional survey among antenatal attendees
Authors: Byamugisha Robert , Tumwine James K , Ndeezi Grace , Karamagi Charles AS , Tylleskär Thorkild 
Published: January 2011

BackgroundHIV testing rates have exceeded 90% among the pregnant women at Mbale Regional Referral Hospital in Mbale District, eastern Uganda, since the introduction of routine antenatal counselling and testing for HIV in June 2006. However, no documented information was available about opinions of pregnant women in eastern Uganda about this HIV testing approach. We therefore conducted a study to assess attitudes of antenatal attendees towards routine HIV counselling and testing at Mbale Hospital. We also assessed their knowledge about mother to child transmission of HIV and infant feeding options for HIV‐infected mothers.MethodsThe study was a cross‐sectional survey of 388 women, who were attending the antenatal clinic for the first time with their current pregnancy at Mbale Regional Referral Hospital from August to October 2009. Data were collected using a pre‐tested questionnaire and analysed using descriptive statistics and logistic regression. Permission to conduct the study was obtained from the Makerere University College of Health Sciences, the Uganda National Council of Science and Technology, and Mbale Hospital.ResultsThe majority of the antenatal attendees (98.5%, 382/388) had positive attitudes towards routine HIV counselling and testing, and many of them (more than 60%) had correct knowledge of how mother to child transmission of HIV could occur during pregnancy, labour and through breastfeeding, and ways of preventing it. After adjusting for independent variables, having completed secondary school (odds ratio: 2.5, 95% confidence interval: 1.3‐4.9), having three or more pregnancies (OR: 2.5, 95% CI: 1.4‐4.5) and belonging to a non‐Bagisu ethnic group (OR: 1.7, 95% CI: 1.0‐2.7) were associated with more knowledge of exclusive breastfeeding as one of the measures for prevention of mother to child transmission of HIV. Out of 388 antenatal attendees, 386 (99.5%) tested for HIV and 382 (98.5%) received same‐day HIV test results.ConclusionsRoutine offer of antenatal HIV counselling and testing is largely acceptable to the pregnant women in eastern Uganda and has enabled most of them to know their HIV status as part of the prevention of mother to child transmission of HIV package of services. Our findings call for further strengthening and scaling up of this HIV testing approach in many more antenatal clinics countrywide in order to maximize its potential benefits to the population.
Keeping health staff healthy: evaluation of a workplace initiative to reduce morbidity and mortality from HIV/AIDS in Malawi
Authors: Bemelmans Marielle , van den Akker Thomas , Pasulani Olesi , Tayub Nabila Saddiq , Hermann Katharina , Mwagomba Beatrice , Jalasi Winnie , Chiomba Harriet , Ford Nathan , Philips Mit 
Published: January 2011

BackgroundIn Malawi, the dramatic shortage of human resources for health is negatively impacted by HIV‐related morbidity and mortality among health workers and their relatives. Many staff find it difficult to access HIV care through regular channels due to fear of stigma and discrimination. In 2006, two workplace initiatives were implemented in Thyolo District: a clinic at the district hospital dedicated to all district health staff and their first‐degree relatives, providing medical services, including HIV care; and a support group for HIV‐positive staff.MethodsUsing routine programme data, we evaluated the following outcomes up to the end of 2009: uptake and outcome of HIV testing and counselling among health staff and their dependents; uptake and outcomes of antiretroviral therapy (ART) among health staff; and membership and activities of the support group. In addition, we included information from staff interviews and a job satisfaction survey to describe health workers' opinions of the initiatives.ResultsAlmost two‐thirds (91 of 144, 63%) of health workers and their dependents undergoing HIV testing and counselling at the staff clinic tested HIV positive. Sixty‐four health workers had accessed ART through the staff clinic, approximately the number of health workers estimated to be in need of ART. Of these, 60 had joined the support group. Cumulative ART outcomes were satisfactory, with more than 90% alive on treatment as of June 2009 (the end of the study observation period). The availability, confidentiality and quality of care in the staff clinic were considered adequate by beneficiaries.ConclusionsStaff clinic and support group services successfully provided care and support to HIV‐positive health workers. Similar initiatives should be considered in other settings with a high HIV prevalence.
Detection of human cytomegalovirus in normal and neoplastic breast epithelium
Authors: Harkins Lualhati E , Matlaf Lisa A , Soroceanu Liliana , Klemm Katrin , Britt William J , Wang Wenquan , Bland Kirby I , Cobbs Charles S 
Published: January 2011

Abstract

Introduction
Human cytomegalovirus (HCMV) establishes a persistent life-long infection, and can cause severe pathology in the fetus and the immunocompromised host[1]. Breast milk is the primary route of transmission in humans worldwide, and breast epithelium is thus a likely site of persistent infection and/or reactivation, though this phenomenon has not previously been demonstrated. Increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. We hypothesized that persistent HCMV infection occurs in normal adult breast epithelium and that persistent viral expression might be associated with normal and neoplastic ductal epithelium.

Methods
Surgical biopsy specimens of normal breast (n = 38) breast carcinoma (n = 39) and paired normal breast from breast cancer patients (n = 21) were obtained. Specimens were evaluated by immunohistochemistry, in situ hybridization, PCR and DNA sequencing for evidence of HCMV antigens and nucleic acids.

Results
We detected HCMV expression specifically in glandular epithelium in 17/27 (63%) of normal adult breast cases evaluated. In contrast, HCMV expression was evident in the neoplastic epithelium of 31/32 (97%) patients with ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) cases evaluated (p = 0.0009).

Conclusions
These findings are the first to demonstrate that persistent HCMV infection occurs in breast epithelium in a significant percentage of normal adult females. HCMV expression was also evident in neoplastic breast epithelium in a high percentage of normal and neoplastic breast tissues obtained from breast cancer patients, raising the possibility that viral infection may be involved in the neoplastic process.
RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1
Authors: Zhao Ming , Wu Xiaoyan , Zhang Qing , Luo Shuangyan , Liang Gongping , Su Yuwen , Tan Yixin , Lu Qianjin 
Published: January 2011

Abstract
Introduction
Regulatory factor X-box 1 (RFX1) can interact with DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1), and RFX1 down-regulation contributes to DNA hypomethylation and histone H3 hyperacetylation at the cluster of differentiation (CD) 11a and CD70 promoters in CD4+ T cells of patients with systemic lupus erythematosus (SLE). This leads to CD11a and CD70 overexpression, thereby triggering autoimmune responses. In order to provide more insight into the epigenetic mechanisms leading to the deregulation of autoimmune-related genes in SLE, we asked whether RFX1 is involved in regulating histone 3 lysine 9 (H3K9) tri-methylation at the CD11a and CD70 promoters in SLE CD4+ T cells.

Methods
CD4+ T cell samples were isolated from 15 SLE patients and 15 healthy controls. H3K9 tri-methylation levels were measured by chromatin immunoprecipitation (ChIP) and real-time quantitative PCR. CD4+ T cells were transfected with plasmids using the Human T cell Nucleofector Kit. RFX1 and histone methyltransferase suppressor of variegation 3-9 (Drosophila) homolog 1 (SUV39H1) interaction was determined by co-immunoprecipation (co-IP) and Western blot and immunofluorescence staining. CD11a and CD70 mRNA levels were measured by real-time RT-PCR.

Results
H3K9 tri-methylation levels were significantly reduced within the CD11a and CD70 promoter regions in SLE CD4+ T cells. RFX1 co-immunoprecipitated with SUV39H1 at the CD11a and CD70 promoters in healthy control CD4+ T cells. Overexpressing or knocking-down RFX1 revealed that RFX1 expression correlated with H3K9 tri-methylation levels, as well as CD11a and CD70 expression levels in CD4+ T cells.

Conclusions
RFX1 recruits SUV39H1 to the promoter regions of the CD11a and CD70 genes in CD4+ T cells, thereby regulating local H3K9 tri-methylation levels. These findings shed further light on the central role of RFX1 down-regulation in the epigenetic de-repression of auto-immune genes in SLE.
Breast cancer research output, 1945-2008: a bibliometric and density-equalizing analysis
Authors: Glynn Ronan W , Scutaru Cristian , Kerin Michael J , Sweeney Karl J 
Published: January 2011

Abstract
Introduction
Breast cancer is the most common form of cancer among women, with an estimated 194,280 new cases diagnosed in the United States in 2009 alone. The primary aim of this work was to provide an in-depth evaluation of research yield in breast cancer from 1945 to 2008, using large-scale data analysis, the employment of bibliometric indicators of production and quality, and density-equalizing mapping.

Methods
Data were retrieved from the Web of Science (WOS) Science Citation Expanded database; this was searched using the Boolean operator, 'OR', with different terms related to breast cancer, including "breast cancer", "mammary ductal carcinoma" and "breast tumour". Data were then extracted from each file, transferred to Excel charts and visualised as diagrams. Mapping was performed as described by Groneberg-Kloft et al. in 2008.

Results
A total of 180,126 breast cancer-associated items were produced over the study period; these had been cited 4,136,224 times. The United States returned the greatest level of output (n = 77,101), followed by the UK (n = 18,357) and Germany (n = 12,529). International cooperation peaked in 2008, with 3,127 entries produced as a result; relationships between the United States and other countries formed the basis for the 10 most common forms of bilateral cooperation. Publications from nations with high levels of international cooperation were associated with greater average citation rates. A total of 4,096 journals published at least one item on breast cancer, although the top 50 most prolific titles together accounted for over 43% (77,517/180,126) of the total output.

Conclusions
Breast cancer-associated research output continues to increase annually. In an era when bibliometric indicators are increasingly being employed in performance assessment, these findings should provide useful information for those tasked with improving that performance.
A PALB2 mutation associated with high risk of breast cancer
Authors: Southey Melissa C , Teo Zhi L , Dowty James G , Odefrey Fabrice A , Park Daniel J , Tischkowitz Marc , Sabbaghian Nelly , Apicella Carmel , Byrnes Graham B , Winship Ingrid , Baglietto Laura , Giles Graham G , Goldgar David E , Foulkes William D , Hopper John L ,   kConFab,   the Breast Cancer Family Registry
Published: January 2011

Abstract
Introduction
As a group, women who carry germline mutations in partner and localizer of breast cancer 2 susceptibility protein (PALB2) are at increased risk of breast cancer. Little is known about by how much or whether risk differs by mutation or family history, owing to the paucity of studies of cases unselected for family history.

Methods
We screened 1,403 case probands for PALB2 mutations in a population-based study of Australian women with invasive breast cancer stratified by age at onset. The age-specific risk of breast cancer was estimated from the cancer histories of first- and second-degree relatives of mutation-carrying probands using a modified segregation analysis that included a polygenic modifier and was conditioned on the carrier case proband. Further screening for PALB2 c.3113G > A (W1038X) was conducted for 779 families with multiple cases of breast cancer ascertained through family cancer clinics in Australia and New Zealand and 764 population-based controls.

Results
We found five independent case probands in the population-based sample with the protein-truncating mutation PALB2 c.3113G > A (W1038X); 2 of 695 were diagnosed before age 40 years and 3 of 708 were diagnosed when between ages 40 and 59 years. Both of the two early-onset carrier case probands had very strong family histories of breast cancer. Further testing found that the mutation segregated with breast cancer in these families. No c.3113G > A (W1038X) carriers were found in 764 population-based unaffected controls. The hazard ratio was estimated to be 30.1 (95% confidence interval (CI), 7.5 to 120; P < 0.0001), and the corresponding cumulative risk estimates were 49% (95% CI, 15 to 93) to age 50 and 91% (95% CI, 44 to 100) to age 70. We found another eight families carrying this mutation in 779 families with multiple cases of breast cancer ascertained through family cancer clinics.

Conclusions
The PALB2 c.3113G > A mutation appears to be associated with substantial risks of breast cancer that are of clinical relevance.