bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Novel Nasopharyngeal Carcinoma Biomarkers by Laser Capture Microdissection and Proteomic Analysis
Authors: Cheng Ai-Lan , Huang Wei-Guo , Chen Zhu-Chu , Peng Fang , Zhang Peng-Fei , Li Mao-Yu , Li Feng , Li Jian-Ling , Li Cui , Yi Hong , Yi Bin , Xiao Zhi-Qiang 
Published: January 2008

Abstract
Purpose: To identify novel nasopharyngeal carcinoma (NPC) biomarkers by laser capture microdissection and a proteomic approach.
Experimental Design: Proteins from pooled microdissected NPC and normal nasopharyngeal epithelial tissues (NNET) were separated by two-dimensional gel electrophoresis, and differential proteins were identified by mass spectrometry. Expression of three differential proteins (stathmin, 14-3-3σ, and annexin I) in the above two tissues as well as four NPC cell lines was determined by Western blotting. Immunohistochemistry was also done to detect the expression of three differential proteins in 98 cases of primary NPC, 30 cases of NNET, and 20 cases of cervical lymph node metastases, and the correlation of their expression levels with clinicopathologic features and clinical outcomes were evaluated.
Results: Thirty-six differential proteins between the NPC and NNET were identified. The expression levels of stathmin, 14-3-3σ, and annexin I in the two types of tissues were confirmed and related to differentiation degree and/or metastatic potential of the NPC cell lines. Significant stathmin up-regulation and down-regulation of 14-3-3σ and annexin I were observed in NPC versus NNET, and significant down-regulation of 14-3-3σ and annexin I was also observed in lymph node metastasis versus primary NPC. In addition, stathmin up-regulation and down-regulation of 14-3-3σ and annexin I were significantly correlated with poor histologic differentiation, advanced clinical stage, and recurrence, whereas down-regulation of 14-3-3σ and annexin I was also significantly correlated with lymph node and distant metastasis. Furthermore, survival curves showed that patients with stathmin up-regulation and down-regulation of 14-3-3σ and annexin I had a poor prognosis. Multivariate analysis revealed that the expression status of stathmin, 14-3-3σ, and annexin I was an independent prognostic indicator.
Conclusion: The data suggest that stathmin, 14-3-3σ, and annexin I are potential biomarkers for the differentiation and prognosis of NPC, and their dysregulation might play an important role in the pathogenesis of NPC.
Carcinoembryonic Antigen Cell Adhesion Molecule 6 Predicts Breast Cancer Recurrence following Adjuvant Tamoxifen
Authors: Maraqa Loaie , Cummings Michele , Peter Mark B. , Shaaban Abeer M. , Horgan Kieran , Hanby Andrew M. , Speirs Valerie 
Published: January 2008

Abstract
Purpose: Tamoxifen remains therapy of choice for premenopausal estrogen receptor α–positive breast cancer. However, resistance and recurrence are serious problems. Our previous work indicated that carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) was significantly up-regulated in tamoxifen-resistant (TAMr) MCF-7 derivatives. The aim of this study was to determine the functional role of CEACAM6 in endocrine-resistant breast cancer and to retrospectively test whether it was predictive of resistance in a large cohort of breast cancers with long-term follow-up.
Experimental Design: siRNA silencing of CEACAM6 was done in TAMr cells and effects on clonogenicity and endocrine sensitivity were determined. CEACAM6 immunohistochemistry was done on a tissue microarray comprising 108 relapsed primary human breast cancers and 243 tamoxifen-sensitive controls.
Results: siRNA-mediated silencing of CEACAM6 reduced both clonogenicity and anchorage-dependent and anchorage-independent growth of TAMr cells. Importantly, CEACAM6 silencing restored sensitivity of TAMr cells to 4-hydroxytamoxifen and proliferative response to 17β-estradiol. Immunohistochemistry showed significantly more CEACAM expression in the relapsed group compared with nonrelapsed controls [35 of 108 (33.3%) and 32 of 243 (13.2%), respectively; odds ratio, 3.16 (95% confidence interval, 1.83-5.47); P &lt; 0.0001]. Additionally, we derived an outcome predictor model based on CEACAM expression that restratified patients in the Nottingham prognostic index intermediate-risk group into either higher-risk or lower-risk group.
Conclusions: Our data support an important role for CEACAM6 in endocrine resistance, which can serve as a powerful predictor of future recurrence.
Inverse Relationship between Human Papillomavirus-16 Infection and Disruptivep53Gene Mutations in Squamous Cell Carcinoma of the Head and Neck
Authors: Westra William H. , Taube Janis M. , Poeta M.L. , Begum Shanaz , Sidransky David , Koch Wayne M. 
Published: January 2008

AbstractPurpose: Squamous cell carcinomas of the head and neck (HNSCC) often harbor p53 mutations, but p53 protein degradation by the viral oncoprotein E6 may supercede p53 mutations in human papillomavirus 16 (HPV16)–positive tumors. The prevalence of p53 mutations in HPV-positive HNSCCs is indeed lower, but in some tumors these alterations coexist. The purpose of this study was to discern whether HNSCCs differ in the type of p53 mutations as a function of HPV16 status.Experimental Design: The study was nested within a prospective multicenter study (ECOGE 4393/RTOG R9614) of patients with HNSCC treated surgically with curative intent. Tumors from one study center were used to construct a tissue microarray. The tumors were well characterized with respect to p53 mutational status. The tissue microarray was evaluated by HPV16 in situ hybridization. HPV16 analysis was also done on a select group of tonsillar carcinomas known to harbor disruptive p53 mutations defined as stop mutations or nonconservative mutations within the DNA binding domain.Results: HPV16 was detected in 12 of 89 (13%) HNSCCs. By tumor site, HPV16 was detected in 12 of 21 (57%) tumors from the palatine/lingual tonsils, but in none of 68 tumors from nontonsillar sites (P &lt; 0.00001). Both HPV16-positive and HPV16-negative HNSCCs harbored p53 mutations (25% versus 52%), but disruptive mutations were only encountered in HPV16-negative carcinomas. Of seven tonsillar carcinomas with disruptive p53 mutations, none were HPV16 positive, in contrast to HPV16-positive tonsillar carcinomas without disruptive p53 mutations (0% versus 57%; P = 0.008).Conclusions: Although HPV16 and mutated p53 may coexist in a subset of HNSCCs, HPV16 and disruptive p53 mutations seem to be nonoverlapping events. A less calamitous genetic profile, including the absence of disruptive p53 mutations, may underlie the emerging clinical profile of HPV16-positive HNSCC such as improved patient outcome.
STX140 Is Efficacious In vitro and In vivo in Taxane-Resistant Breast Carcinoma Cells
Authors: Newman Simon P. , Foster Paul A. , Stengel Chloe , Day Joanna M. , Ho Yaik T. , Judde Jean-Gabriel , Lassalle Myriam , Prevost Gregoire , Leese Mathew P. , Potter Barry V.L. , Reed Michael J. , Purohit Atul 
Published: January 2008

Abstract
Purpose: The aim of these studies was to characterize the action of STX140 in a P-glycoprotein–overexpressing tumor cell line both in vitro and in vivo. In addition, its efficacy was determined against xenografts derived from patients who failed docetaxel therapy.
Experimental Design: The effects of STX140, Taxol, and 2-methoxyestradiol (2-MeOE2) on cell proliferation, cell cycle, and apoptosis were assessed in vitro in drug-resistant cells (MCF-7DOX) and the parental cell line (MCF-7WT). Mice bearing an MCF-7DOX tumor on one flank and an MCF-7WT tumor on the other flank were used to assess the in vivo efficacy. Furthermore, the responses to STX140 of three xenografts, derived from drug-resistant patients, were assessed.
Results: In this study, STX140 caused cell cycle arrest, cyclin B1 induction, and subsequent apoptosis of both MCF-7DOX and MCF-7WT cells. Taxol and 2-MeOE2 were only active in the MCF-7WT parental cell line. Although both STX140 and Taxol inhibited the growth of xenografts derived from MCF-7WT cells, only STX140 inhibited the growth of tumors derived from MCF-7DOX cells. 2-MeOE2 was ineffective at the dose tested against both tumor types. Two out of the three newly derived docetaxel-resistant xenografts, including a metastatic triple-negative tumor, responded to STX140 but not to docetaxel treatment.
Conclusions: STX140 shows excellent efficacy in both MCF-7WT and MCF-7DOX breast cancer xenograft models, in contrast to Taxol and 2-MeOE2. The clinical potential of STX140 was further highlighted by the efficacy seen in xenografts recently derived from patients who had failed on taxane therapy.
Predicting Outcome in Follicular Lymphoma by Using Interactive Gene Pairs
Authors: LeBrun David , Baetz Tara , Foster Cheryl , Farmer Patricia , Sidhu Roger , Guo Hong , Harrison Karen , Somogyi Roland , Greller Larry D. , Feilotter Harriet 
Published: January 2008

Abstract
Purpose: Follicular lymphoma is a common lymphoma of adults. Although its course is often indolent, a substantial proportion of patients have a poor prognosis, often due to rapid progression or transformation to a more aggressive lymphoma. Currently available clinical prognostic scores, such as the follicular lymphoma international prognostic index, are not able to optimally predict transformation or poor outcome.
Experimental Design: Gene expression profiling was done on primary lymphoma biopsy samples.
Results: Using a statistically conservative approach, predictive interaction analysis, we have identified pairs of interacting genes that predict poor outcome, measured as death within 5 years of diagnosis. The best gene pair performs &gt;1,000-fold better than any single gene or the follicular lymphoma international prognostic index in our data set. Many gene pairs achieve outcome prediction accuracies exceeding 85% in extensive cross-validation and noise sensitivity computational analyses. Many genes repeatedly appear in top-ranking pairs, suggesting that they reproducibly provide predictive capability.
Conclusions: The evidence reported here may provide the basis for an expression-based, multi-gene test for predicting poor follicular lymphoma outcomes.
Image-Guided Enzyme/Prodrug Cancer Therapy
Authors: Li Cong , Penet Marie-France , Winnard Paul , Artemov Dmitri , Bhujwalla Zaver M. 
Published: January 2008

Abstract
Purpose: The success of enzyme/prodrug cancer therapy is limited by the uncertainty in the delivery of the enzyme in vivo. This study shows the use of noninvasive magnetic resonance (MR) and optical imaging to image the delivery of a prodrug enzyme. With this capability, prodrug administration can be timed so that the enzyme concentration is high in the tumor and low in systemic circulation and normal tissue, thereby minimizing systemic toxicity without compromising therapeutic efficiency.
Experimental Design: The delivery of a multimodal imaging reporter functionalized prodrug enzyme, cytosine deaminase, was detected by MR and optical imaging in MDA-MB-231 breast cancer xenografts. Stability of the enzyme in the tumor was verified by 19F MR spectroscopy, which detected conversion of 5-fluorocytosine to 5-flurouracil. The optimal time window for prodrug injection determined by imaging was validated by immunohistochemical, biodistribution, and high-performance liquid chromatographic studies. The therapeutic effect and systemic toxicity of this treatment strategy were investigated by histologic studies and tumor/body weight growth curves.
Results: The delivery of the functionalized enzyme in tumors was successfully imaged in vivo. The optimal time window for prodrug administration was determined to be 24 h, at which time the enzyme continued to show high enzymatic stability in tumors but was biodegraded in the liver. Significant tumor growth delay with tolerable systemic toxicity was observed when the prodrug was injected 24 h after the enzyme.
Conclusion: These preclinical studies show the feasibility of using a MR-detectable prodrug enzyme to time prodrug administration in enzyme/prodrug cancer therapy.
Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells
Authors: Dai Yun , Chen Shuang , Kramer Lora B. , Funk Vanessa L. , Dent Paul , Grant Steven 
Published: January 2008

Abstract
Purpose: The goal of this study was to characterize interactions between the proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors (HDACI) romidepsin or belinostat in chronic lymphocytic leukemia (CLL) cells.
Experimental Design: Primary and cultured (JVM-3 and MEC-2) CLL cells were exposed to agents alone or in combination, after which cell death was determined by 7-aminoactinomycin D staining/flow cytometry. Acetylation of target proteins, activation of caspase cascades, and expression of apoptosis-regulatory proteins were monitored by Western blot analysis. Nuclear factor-κB (NF-κB) activity was determined by luciferase reporter assay. Cells were transiently transfected with wild-type and acetylation site-mutated (inactive) RelA(p65) (e.g., K221R, K310R, or K281/221/310R) and assessed for HDACI sensitivity.
Results: Combined exposure to very low concentrations of romidepsin or belinostat (i.e., low nanomolar and submicromolar, respectively) in combination with low nanomolar concentrations of bortezomib synergistically induced cell death in primary and cultured CLL cells. These events were likely associated with prevention of HDACI-mediated RelA acetylation and NF-κB activation by bortezomib, down-regulation of antiapoptotic proteins (i.e., Bcl-xL, Mcl-1, and XIAP), as well as up-regulation of the proapoptotic protein Bim, resulting in activation of caspase cascade. Finally, CLL cells transfected with inactive RelA displayed a significant increase in HDACI lethality.
Conclusions: Coadministration of the clinically relevant HDACIs romidepsin or belinostat with bortezomib synergistically induces cell death in CLL cells, likely through mechanisms involving, among other factors, NF-κB inactivation and perturbation in the expression of proapoptotic and antiapoptotic proteins. A strategy combining HDAC with proteasome inhibition warrants further attention in CLL.
Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy
Authors: Friday Bret B. , Adjei Alex A. 
Published: January 2008

Abstract
The identification of intracellular signaling cascades important for the growth and survival of cancer cells has led to the development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently, several small-molecule inhibitors of MAPK/extracellular signal–regulated kinase kinase (MEK), a key intermediary of MAPK signaling, have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development of small-molecule MEK inhibitors, and the results obtained to date with MEK inhibitors in human cancer trials.
Nematodes of the order Dorylaimida from Romania. The genus Thonus Thorne, 1974. Part II
Authors: Ciobanu Marcel , Peña-Santiago Reyes , Popovici Iuliana , Abolafia Joaquin 
Published: January 2008

AbstractFive Thonus species from Romania are described. Thonus montanus sp. n. is characterised by its body length of 1.56-1.90 mm, cuticle with coarse transverse striations, lip region 15-18 μm diam., odontostyle 20-22.5 μm long, plicate guiding ring, neck 400-553 μm long, pharyngeal expansion occupying 49-56% of total neck length, uterus 1-1.5 body diam. long, pars refringens vaginae with two separate pieces, gland cells present near vagina-vulva junction, vulva a short post-equatorial (V = 54-59) longitudinal slit, and female tail conoid (25-33 μm, c = 54-73, c′ = 0.8-1.2) with abundant blister-like structures and distinct hyaline portion. Thonus tenuistylus sp. n. is characterised by its body length of 1.17-1.56 mm, lip region offset by a more or less, usually well, marked constriction and 16-17.5 μm diam., slender odontostyle 17-20.5 μm long or 1.1-1.3 times lip region diam., neck 275-397 μm long, pharyngeal expansion occupying 42-52% of total neck length, female genital system amphidelphic, uterus bipartite and 1.7-2 body diam. long, pars refringens vaginae with two adjacent pieces, vulva a post-equatorial (V = 50-56) transverse slit, tail conoid-rounded (19-24 μm, c = 48.7-72.9, c′ = 0.8-1.0) and with abundant blister-like structures, spicules 38-43 μm long, and 3-6 widely spaced ventromedian supplements. Thonus sp. is characterised by its slender (a = 37.5) body 1.41 mm long, lip region practically continuous with adjacent body and 11.5 μm diam., odontostyle 10.5 μm long, neck 325 μm long, pharyngeal expansion 138 μm long or ca two-fifths of total neck length, a coarse ring-like structure surrounding cardia, female genital system amphidelphic, uterus ca 2.5 body diam. long, pars refringens vaginae with two adjacent trapezoidal pieces, vulva a transverse slit (V = 52), a pseudocoelomocyte present at mid-body, tail convex conoid (26.5 μm, c = 56, c′ = 1.1) with abundant blister-like structures, and males unknown. Thonus eroshenkoi n. comb. and T. medianus n. comb. are proposed. Thonus kaszabi and T. medianus n. comb. are new records for the Romanian nematode fauna.
Cover crops and organic mulches for nematode, weed and plant health management
Authors: Wang Koon-Hui , Kokalis-Burelle Nancy , McSorley Robert , Gallaher Raymond 
Published: January 2008

AbstractTraditional cover cropping systems for nematode management seldom consider weed and soil nutrient management concurrently. Integrating cover crops suppressive to plant-parasitic nematodes with a cover crop mulching system could improve traditional approaches. Two field experiments were conducted in 2003 and 2004 to evaluate 'Tropic Sun' sunn hemp (Crotalaria juncea) and 'Iron Clay' cowpea (Vigna unguiculata) as summer cover crops and as organic mulches. Both experiments were in a 3 × 3 split-plot design in which the main plots were summer planting of sunn hemp, cowpea or fallow, and the subplots were organic mulch of sunn hemp, cowpea or no mulch. The summer cover crop was followed by turnip (Brassica rapa) and lima bean (Phaseolus lunatus) in the autumn. Using sunn hemp as organic mulch suppressed root-knot nematodes more effectively than using it as a cover crop, but only on a less susceptible host such as turnip, and not on a very susceptible host such as lima bean. While sunn hemp as a cover crop failed to enhance beneficial free-living nematodes, sunn hemp as an organic mulch enhanced bacterial-feeding nematode population densities. Sunn hemp mulch also suppressed broadleaf weeds but not grasses or nutsedges. Although sunn hemp and cowpea cover crops did not increase lima bean N and K content, their mulches increased N and K content. Similar results were observed for turnip and lima bean yields. Population density of root-knot nematodes was positively related to abundance of omnivorous nematode in 2003. The abundance of plant-parasitic nematodes was negatively related to the infestation levels of Pasteuria penetrans, and the abundance of predatory nematodes in 2004. Factors that might have affected the performance of sunn hemp on nematode communities are discussed.
What Makes a Good City? Reflections on Urban Life and Faith
Authors: Graham Elaine 
Published: January 2008

AbstractThis article is a case study in public theology, drawing on the author's experience as a member of the Church of England's Commission on Urban Life and Faith (CULF). Following in the footsteps of the seminal Archbishops' Commission on Urban Priority Areas (ACUPA) report, Faith in the City (1985), CULF aimed to evaluate the future of the urban church and its role in the local community, arguing that the impact of faith-based organizations constituted a major contribution to local community empowerment and well-being. CULF coined the term 'faithful capital' (after Robert Putnam's concept of 'social capital') to express the added value that people of faith contribute to their local communities, and called for wider debate around the question 'what makes a good city?' This article also scrutinizes the Commission's theological method, and in particular its attempt to model a form of 'theology from below'; and in the light of the Commission's findings, poses questions for the future of public theology.
Super-Sizing Community Development Initiatives: The Case of Hillbrow's Faith Sector
Authors: Winkler Tanja 
Published: January 2008

AbstractGrowing efforts by religious communities to pursue political goals have directed scholarly attention to their role as potential antipoverty and development agents in local settings. Yet agents are organized in a myriad of ways. Some forge alliances across traditional boundaries via 'bridging' mechanisms; others defend particularistic interests by adopting 'barrier' strategies. The former, however, is more likely to lead to the social transformation of poor neighbourhoods. Accordingly, in Johannesburg's most stressed inner-city neighbourhood, Hillbrow, sites of faith-based activities have become 'spaces of hope' for approximately seventy percent of its residents and at least eight faith-based organizations (FBOs) facilitate social and welfare programmes abandoned by the City Council. Here, despite the implementation of community development projects, poverty and hardship prevail. This article seeks to investigate reasons for developmental fragmentation by researching the institutional and political cultures of Hillbrow's FBOs and the City of Johannesburg.
A Multi-level Approach to the Study of the Seal Impressions
Authors: Messina Vito 
Published: January 2008

AbstractRecent discovery of clay-sealings and clay-tablets' hoards in ancient sites from the Mediterranean countries to the Indian Subcontinent enriched the acquired knowledge on seal impressions. Excavations brought to light new statistic and extrinsic data: the need of a complex analysis of the seal impressions is the direct consequence of the increased information and a new approach has been defined during specific studies. The current trend is to discriminate between intrinsic and extrinsic data by defining the different levels of information. The aim of this paper is to point by selected examples to the results of some recent works and to focus on the new multi-level approach to the study of seal impressions.
The Mass Repatriation of the Armenians from Iran in 1946-1947 (Some Statistical Data)
Authors: Malekian Lina 
Published: January 2008

AbstractAfter the independence of Armenia following the disintegration of the USSR in 1991, most of hitherto closed archive materials became accessible for wide scholarship. This paper is an attempt to present a statistical analysis of the data concerning the Armenian migrants from Iran during a mass repatriation in 1946-1947. It is based mainly on the archive documents preserved in the Armenian National Archives in Yerevan. The paper provides detailed information on various demographical parameters of the repatriates including gender, age, profession, marital status, education level, employment, and literacy.
Return Periods of Continental U.S. Hurricanes
Authors: Parisi Francis , Lund Robert 
Published: January 2008

AbstractThis note estimates return periods of Atlantic basin hurricanes striking the continental United States. With Hurricane Katrina fresh on the public’s mind, there is considerable interest in this topic. The return periods are estimated from historical data from the 1900 to 2006 period via extreme value methods and Poisson regression techniques. Despite the recent active 2004 and 2005 hurricane seasons, the authors do not find evidence of an increasing trend in hurricane strike frequencies.