bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Spectral Imaging: Improving Colposcopy
Authors: Soutter William P. , Diakomanolis Emmanuel , Lyons Deirdre , Ghaem-Maghami Sadaf , Ajala Tosin , Haidopoulos Dimitrios , Doumplis Dimitrios , Kalpaktsoglou Costas , Sakellaropoulos Gerasimos , Soliman Suzan , Perryman Karen , Hird Vicky , Buckley C. Hilary , Pavlakis Kitty , Markaki Sofia , Dina Roberto , Healy Vourneen , Balas Costas 
Published: February 2009

Abstract
Purpose: Colposcopy occupies a key role in the prevention of cervical cancer by identifying preinvasive or invasive lesions. However, colposcopy is subjective and is responsible for 52% of screening failures. Dynamic spectral imaging (DSI) is based on the objective, quantitative assessment of the acetowhitening effect. This study compared DSI with colposcopy.
Experimental Design: Women referred for colposcopy were examined simultaneously with colposcopy and DSI using a precommercial DySIS model (FPC-03) in an international, multicenter trial. The colposcopy impression and DySIS values were compared with consensus histology reports of biopsies. Subjects were recruited to a training group and subsequently to a test group. Measures were taken to avoid verification bias.
Results: The training and test groups comprised 82 and 308 eligible women, respectively. A cutoff value to identify high-grade disease was selected from the results of the training group and data from previous work. Receiver operator curve analysis of the test data showed an area under the curve of 0.844. DySIS detected 62.9% more high-grade cases than colposcopy (57 versus 35, P = 0.0001). DySIS exceeded end points approved by the Food and Drug Administration for similar studies, with increments in the true positive rate of 22/308 (7.1%; lower 95% CL, 4.5% versus 2%) and in the false positive rate of 32/308 (10.4%; upper 95% CL, 14.7% versus 15%).
Conclusions: DySIS is more sensitive than colposcopy in detecting high-grade lesions and can provide improved guidance for biopsy. The results are obtained in a user-independent fashion, making it suitable for use by nursing personnel.
Unique Methylation Pattern of Oncostatin M Receptor Gene in Cancers of Colorectum and Other Digestive Organs
Authors: Deng Guoren , Kakar Sanjay , Okudiara Keisuke , Choi Esther , Sleisenger Marvin H. , Kim Young S. 
Published: February 2009

Abstract
Purpose: Oncostatin M (OSM) is an interleukin-6 cytokine family member, which inhibits cell proliferation and induces cell differentiation and apoptosis in cancers. In melanoma cells, epigenetic silencing of OSM receptor (OSMR) by histone deacetylation contributes to escape of cell growth control by OSM. However, the silencing of OSMR by DNA methylation in any cancer has not been examined.
Experimental Design: Methylation status of OSMR was determined by sequencing or methylation-specific PCR in primary tumors and cell lines. Cell lines were treated with DNA methyltransferase inhibitors 5-aza-2-deoxycytidine or DNA methyltransferase 1 small interfering RNA or a histone deacetylase inhibitor trichostatin A. OSMR mRNA level was determined by reverse transcription-PCR. The acetylation of histone H3 was analyzed by chromatin immunoprecipitation assay.
Results: We observed methylation of OSMR in 88 of 98 (90%) colorectal cancers, 34 of 38 (89%) colorectal polyps, 17 of 31 (55%) normal-appearing mucosa adjacent to colorectal cancers, 13 of 40 (33%) gastric cancers, and 2 of 10 (20%) pancreatic cancers. OSMR methylation was absent or rarely detected in normal colonic mucosa from noncancer patients or in cancers of nondigestive organs, including breast, lung, liver, prostate, kidney, and melanoma. We observed a significant correlation between OSMR methylation and loss of mRNA expression in 39 cancer cell lines. Following the treatment of colorectal cancer cell lines with 5-aza-2-deoxycytidine, DNA methyltransferase 1 small interfering RNA, or trichostatin A, the induction of OSMR mRNA and the enrichment in the level of histone acetylation were observed.
Conclusions: The epigenetic silencing and DNA methylation of OSMR occur frequently in colorectal cancers and rarely in cancers of nondigestive organs. OSMR methylation is an early event in the colorectal carcinogenesis.
NRH:Quinone Oxidoreductase 2-Deficient Mice Are Highly Susceptible to Radiation-Induced B-Cell Lymphomas
Authors: Iskander Karim , Barrios Roberto J. , Jaiswal Anil K. 
Published: February 2009

Abstract
Purpose: NRH:quinone oxidoreductase 2 (NQO2) is known to protect against myelogenous hyperplasia. However, the role of NQO2 in prevention of hematologic malignancies remains unknown. Present studies investigated in vivo role of NQO2 in prevention of myeloproliferative disease and lymphomas.
Experimental Design: Wild-type and NQO2-null mice were exposed to 0, 1, and 3 Gy γ-radiation. One year later, the mice were analyzed for the development of myeloproliferative disease and lymphomas. Immunohistochemistry analysis determined the B- and T-cell origin of lymphomas. The mice were also sacrificed at 6 and 48 h after radiation exposure and bone marrow was collected and analyzed for p53, Bax, and B-cell apoptosis. Bone marrow cells were cultured and the rate of degradation of p53 was analyzed.
Results: Seventy-two percent NQO2-null mice showed development of B-cell lymphomas in multiple tissues compared with 11% in wild-type mice exposed to 3 Gy γ-radiation. In contrast, only 22% NQO2-null mice showed myeloproliferation compared with none in wild-type mice. Further analysis revealed that bone marrow from NQO2-null mice contained lower levels of p53 compared with wild-type mice due to rapid degradation of p53. In addition, the exposure to radiation resulted in lower induction of p53 and Bax and decreased B-cell apoptosis in NQO2-null mice.
Conclusion: NQO2-null mice are highly susceptible to develop radiation-induced B-cell lymphomas. The lack of significant induction of p53 and Bax and decrease in B-cell apoptosis presumably contributed to the development of lymphomas. NQO2 functions as endogenous factor in prevention against radiation-induced B-cell lymphomas.
Short Pigment Epithelial-Derived Factor-Derived Peptide Inhibits Angiogenesis and Tumor Growth
Authors: Mirochnik Yelena , Aurora Arin , Schulze-Hoepfner Frank T. , Deabes Ahmed , Shifrin Victor , Beckmann Richard , Polsky Charles , Volpert Olga V. 
Published: February 2009

Abstract
Purpose: Pigment epithelial-derived factor (PEDF) is a potent angiogenesis inhibitor with multiple other functions, some of which enhance tumor growth. Our previous studies mapped PEDF antiangiogenic and prosurvival activities to distinct epitopes. This study was aimed to determine the minimal fragment of PEDF, which maintains antiangiogenic and antitumor efficacy.
Experimental Design: We analyzed antigenicity, hydrophilicity, and charge distribution of the angioinhibitory epitope (the 34-mer) and designed three peptides covering its COOH terminus, P14, P18, and P23. We analyzed their ability to block endothelial cell chemotaxis and induce apoptosis in vitro and their antiangiogenic activity in vivo. The selected peptide was tested for the antitumor activity against mildly aggressive xenografted prostate carcinoma and highly aggressive renal cell carcinoma. To verify that P18 acts in the same manner as PEDF, we used immunohistochemistry to measure PEDF targets, vascular endothelial growth factor receptor 2, and CD95 ligand expression in P18-treated vasculature.
Results: P14 and P18 blocked endothelial cell chemotaxis; P18 and P23 induced apoptosis. P18 showed the highest IC50 and blocked angiogenesis in vivo: P23 was inactive and P14 was proangiogenic. P18 increased the production of CD95 ligand and reduced the expression of vascular endothelial growth factor receptor 2 by the endothelial cells in vivo. In tumor studies, P18 was more effective in blocking the angiogenesis and growth of the prostate cancer than parental 34-mer; in the renal cell carcinoma, P18 strongly decreased angiogenesis and halted the progression of established tumors.
Conclusions: P18 is a novel and potent antiangiogenic biotherapeutic agent that has potential to be developed for the treatment of prostate and renal cancer.
Overexpression of Phosphorylated Mammalian Target of Rapamycin Predicts Lymph Node Metastasis and Prognosis of Chinese Patients with Gastric Cancer
Authors: Yu Guanzhen , Wang Jiejun , Chen Ying , Wang Xi , Pan Jun , Li Gang , Jia Zhiliang , Li Qiang , Yao James C. , Xie Keping 
Published: February 2009

Abstract
Purpose: We determined the expression of mammalian target of rapamycin (mTOR) and its activated form, p-mTOR, in Chinese patients with gastric cancer and its clinical effects and underlying mechanisms.
Experimental Design: Tissue microarray blocks containing gastric cancer tissue and matched noncancer gastric tissue specimens obtained from 1,072 patients were constructed. Expression of total mTOR and p-mTOR in these specimens was analyzed using immunohistochemical studies and confirmed by Western blotting.
Results: The overall rates of total mTOR and p-mTOR overexpression were 50.8% (545 of 1,072) and 46.5% (499 of 1,072), respectively. The p-mTOR overexpression was significantly correlated with total mTOR overexpression. Overexpression of total mTOR protein was significantly correlated with tumor differentiation, T1/T2 tumors, and stage I/II/III disease, whereas p-mTOR overexpression was significantly correlated with lymph node metastasis and all stage disease. The Cox proportional hazards model revealed that the overexpression of p-mTOR, but not total mTOR, was an independent prognostic factor for gastric cancer. The overexpression of p-mTOR also predicted the angiogenic phenotype of human gastric cancer and regulated angiogenesis of gastric cancer cells.
Conclusions: Increased activation of mTOR is frequent in human gastric cancer and overexpression of p-mTOR is an independent prognostic factor, suggesting that mTOR pathway could be a potential target for therapy of this malignancy.
Suppression of Tumor GrowthIn vivoby the Mitocan α-tocopheryl Succinate Requires Respiratory Complex II
Authors: Dong Lan-Feng , Freeman Ruth , Liu Ji , Zobalova Renata , Marin-Hernandez Alvaro , Stantic Marina , Rohlena Jakub , Valis Karel , Rodriguez-Enriquez Sara , Butcher Bevan , Goodwin Jacob , Brunk Ulf T. , Witting Paul K. , Moreno-Sanchez Rafael , Scheffler Immo E. , Ralph Stephen J. , Neuzil Jiri 
Published: February 2009

AbstractPurpose: Vitamin E analogues are potent novel anticancer drugs. The purpose of this study was to elucidate the cellular target by which these agents, represented by α-tocopoheryl succinate (α-TOS), suppress tumors in vivo, with the focus on the mitochondrial complex II (CII).Experimental Design: Chinese hamster lung fibroblasts with functional, dysfunctional, and reconstituted CII were transformed using H-Ras. The cells were then used to form xenografts in immunocompromized mice, and response of the cells and the tumors to α-TOS was studied.Results: The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to α-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to α-TOS. Thus, growth of CII-functional and CII-reconstituted tumors was strongly suppressed by the agent, and this was accompanied by high level of apoptosis induction in the tumor cells. On the other hand, α-TOS did not inhibit the CII-dysfuntional tumors.Conclusions: We document in this report a novel paradigm, according to which the mitochondrial CII, which rarely mutates in human neoplasias, is a plausible target for anticancer drugs from the group of vitamin E analogues, providing support for their testing in clinical trials.
Psoralidin, an Herbal Molecule, Inhibits Phosphatidylinositol 3-Kinase–Mediated Akt Signaling in Androgen-Independent Prostate Cancer Cells
Authors: Kumar Raj , Srinivasan Sowmyalakshmi , Koduru Srinivas , Pahari Pallab , Rohr Jürgen , Kyprianou Natasha , Damodaran Chendil 
Published: February 2009

Abstract
The protein kinase Akt plays an important role in cell proliferation and survival in many cancers, including prostate cancer. Due to its kinase activity, it serves as a molecular conduit for inhibiting apoptosis and promoting angiogenesis in most cell types. In most of the prostate tumors, Akt signaling is constitutively activated due to the deletion or mutation of the tumor suppressor PTEN, which negatively regulates phosphatidylinositol 3-kinase through lipid phosphatase activity. Recently, we identified a natural compound, psoralidin, which inhibits Akt phosphorylation, and its consequent activation in androgen-independent prostate cancer (AIPC) cells. Furthermore, ectopic expression of Akt renders AIPC cells resistant to chemotherapy; however, psoralidin overcomes Akt-mediated resistance and induces apoptosis in AIPC cells. While dissecting the molecular events, both upstream and downstream of Akt, we found that psoralidin inhibits phosphatidylinositol 3-kinase activation and transcriptionally represses the activation of nuclear factor-κB and its target genes (Bcl-2, Survivin, and Bcl-xL, etc.), which results in the inhibition of cell viability and induction of apoptosis in PC-3 and DU-145 cells. Interestingly, psoralidin selectively targets cancer cells without causing any toxicity to normal prostate epithelial cells. In vivo xenograft assays substantiate these in vitro findings and show that psoralidin inhibits prostate tumor growth in nude mice. Our findings are of therapeutic significance in the management of prostate cancer patients with advanced or metastatic disease, as they provide new directions for the development of a phytochemical-based platform for prevention and treatment strategies for AIPC.
Linguistic and Stylistic Notes to the Hazon Gabriel Inscription
Authors: Rendsburg Gary 
Published: February 2009

AbstractThis article presents four notes on the recently discovered Hazon Gabriel inscription. Attention is paid to (1) the word in line 24; (2) the phrase in line 77; (3) the presence of alliteration in the text; and (4) the use of variation, especially in the assorted "thus says YHWH" phrases present throughout the composition.
Inclusivism at Qumran
Authors: Holtz Gudrun 
Published: February 2009

AbstractWithin Early Judaism the Qumran Community is widely perceived as a strictly exclusivist group. A thorough analysis of Qumran texts, however, reveals, apart from the dominant strand of exclusivism, remarkably clear inclusivist tendencies. In Qumran literature inclusivist tendencies can be seen both in eschatological texts and in materials dealing with the self-understanding of the Qumran Community in historical time. The legal texts discussed basically confirm this pattern: the Community is to separate from Gentiles and from members of those Jewish groups with whom it earlier entertained close relations. At the same time it is to support the poor and the proselytes. Strictly legal statements prohibiting contacts with non-Essene Judaism as such are missing. In the literature discussed inclusivist and exclusivist tendencies have diff erent weight. A pan-Israelite, e.g. inclusivist, perspective can be seen in 4QpNah, 4QFlor, 4QSM and especially in 4QMMT, 1QSa, and CD/4QD whereas in 1QS exclusivist tendencies predominate.
Measuring Justin's Approach to the Spirit: Trinitarian Conviction and Binitarian Orientation
Authors: Briggman Anthony 
Published: February 2009

AbstractOver the last hundred years scholars have debated the degree to which Justin Martyr distinguishes the activity and identity of the Word and the Spirit. The incomplete analyses of previous studies did not perceive Justin's regular failure to distinguish the activity of the Spirit from that of the Word, which reveals the presence of a binitarian orientation. In addition, combining the work of E.R. Goodenough and C. Oeyen permits us to recognize the presence of a Spirit-Christology in 1 Apol 33 and Dial 87-88. The failure to distinguish the identities of the Word and the Spirit in these two passages are instances in which Justin subordinates his Trinitarian convictions to binitarian logic.
Islamic Finance and Dispute Resolution: Part 1
Authors: Nadar Aisha 
Published: February 2009

AbstractThe Islamic Financial Industry is an industry that organises financial services in accordance with Islamic Law, in the same way as the traditional financial industry is organised in accordance with secular law. The unique challenges facing the industry in terms of compliance with Islamic law have been internationally recognised in relation to capital adequacy, risk management, corporate governance, transparency and disclosure. The same, however, has not been true in the area of dispute resolution. The purpose of this paper is to identify the unique challenges facing Islamic finance in compliance with Islamic law in the ambit of English courts, evaluate the features of international commercial arbitration as they relate to overcoming these challenges, and provide some suggestions for going forward. The paper is structured as follows: Section 1 will be used to introduce Islamic finance and frame the issues facing the industry in relation to dispute resolution. Section 2 will focus on providing the background required, while Section 3 frames Islamic finance in relation to conventional finance. Section 4 will provide an insight into Islamic law.
Respect for Party Autonomy under Current Saudi Arbitration Law
Authors: Al-Fadhel Faisal 
Published: February 2009

AbstractArbitration is an important means for settling disputes between commercial parties, in parallel with the general judicial system. Certain basic standards, such as party autonomy and the supportive role of courts, are required in any modern arbitral legislation if it is to prove effective. This article will focus on the principle of party autonomy, fundamental to modern law, under the current Saudi Arbitration Law. Several issues will be discussed and constructive recommendations given regarding: the consistency in terminology used, specifically with respect to "arbitration instrument", "arbitration clause" and "submission agreement"; the professional qualifications and experience of arbitrators; the choice of language for international arbitration; woman's role as arbitrator; the status of non-Muslim arbitrators; and modernisation of the Saudi Arbitration Law of 1983 and its Implementing Regulations of 1985.
Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study
Authors: Schmiegelow Kjeld , Al-Modhwahi Ibrahim , Andersen Mette Klarskov , Behrendtz Mikael , Forestier Erik , Hasle Henrik , Heyman Mats , Kristinsson Jon , Nersting Jacob , Nygaard Randi , Svendsen Anne Louise , Vettenranta Kim , Weinshilboum Richard 
Published: February 2009

AbstractAmong 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m2; P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.
Cloning, characterization and expression analysis of porcine microRNAs
Authors: Reddy Alavala Matta , Zheng Yun , Jagadeeswaran Guru , Macmil Simone L , Graham Wiley B , Roe Bruce A , Desilva Udaya , Zhang Weixiong , Sunkar Ramanjulu 
Published: February 2009

Abstract

Background
MicroRNAs (miRNAs) are small ~22-nt regulatory RNAs that can silence target genes, by blocking their protein production or degrading the mRNAs. Pig is an important animal in the agriculture industry because of its utility in the meat production. Besides, pig has tremendous biomedical importance as a model organism because of its closer proximity to humans than the mouse model. Several hundreds of miRNAs have been identified from mammals, humans, mice and rats, but little is known about the miRNA component in the pig genome. Here, we adopted an experimental approach to identify conserved and unique miRNAs and characterize their expression patterns in diverse tissues of pig.

Results
By sequencing a small RNA library generated using pooled RNA from the pig heart, liver and thymus; we identified a total of 120 conserved miRNA homologs in pig. Expression analysis of conserved miRNAs in 14 different tissue types revealed heart-specific expression of miR-499 and miR-208 and liver-specific expression of miR-122. Additionally, miR-1 and miR-133 in the heart, miR-181a and miR-142-3p in the thymus, miR-194 in the liver, and miR-143 in the stomach showed the highest levels of expression. miR-22, miR-26b, miR-29c and miR-30c showed ubiquitous expression in diverse tissues. The expression patterns of pig-specific miRNAs also varied among the tissues examined.

Conclusion
Identification of 120 miRNAs and determination of the spatial expression patterns of a sub-set of these in the pig is a valuable resource for molecular biologists, breeders, and biomedical investigators interested in post-transcriptional gene regulation in pig and in related mammals, including humans.