bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of orbital tumors at a comprehensive cancer center in the United States
Authors: Shinder Roman , Al‐Zubidi Nagham , Esmaeli Bita
Published: September 2010

Background.

The purpose of this study was to evaluate the frequencies of various types of orbital lesions seen at a comprehensive cancer center in the United States.

Methods.

In this retrospective case series, we reviewed the medical records of 268 consecutive patients referred to our orbital oncology service for evaluation of an orbital mass between November 1998 and February 2009. Each orbital lesion was documented by CT and/or MRI, and in most cases diagnosis was established with a tissue biopsy. Patients who were seen for second opinions and had inadequate follow‐up data were excluded, as were patients with thyroid eye disease or orbital hemorrhage.

Results.

The study included 134 men and 134 women aged 1 to 89 years at diagnosis (median, 55 years). Follow‐up ranged from 0.06 to 192 months (median, 15 months). Of the tumors, 171 (64%) were primary orbital, 69 (26%) were secondary orbital, and 28 (10%) were metastatic tumors. Lesion types were as follows: secondary orbital tumors, 69 (26%); lymphoproliferative lesions, 68 (25%); metastases, 28 (10%); epithelial lacrimal gland tumors, 27 (10%); inflammatory conditions, 21 (8%); vascular lesions, 20 (7%); mesenchymal tumors, 18 (7%); optic nerve and nerve sheath tumors, 7 (3%); peripheral nerve tumors, 3 (1%); histiocytic lesions, 3 (1%); cystic lesions, 3 (1%); and other lesions, 1 (<1%). The most common histopathologic diagnoses were lymphoma, 50 cases (19%); orbital extension of sinus tumor, 25 (9%); lacrimal gland adenoid cystic carcinoma, 18 (7%); cavernous hemangioma, 15 (6%); orbital extension of brain tumor, 14 (5%); idiopathic orbital inflammation, 14 (5%); plasmacytoma, 8 (3%); reactive lymphoid hyperplasia, 7 (3%); metastatic breast cancer, 7 (3%); orbital extension of ocular adnexal basal cell carcinoma, 7 (3%); orbital extension of ocular adnexal melanoma, 6 (2%), rhabdomyosarcoma, 6 (2%); metastatic gastrointestinal cancer, 5 (2%); sarcoidosis, 5 (2%); and other less common lesions. Forty‐two lesions (16%) were intraconal, and 226 (84%) were extraconal. There were 169 (63%) malignant tumors and 99 (37%) were benign tumors. The rate of malignant lesions was 65% in children and 63% in adults (≥18 years). Malignant conditions encountered at a higher rate than previously reported included lymphoma (19% vs 8% to 13%), secondary orbital tumors (26% vs 13% to 20%), orbital metastases (10% vs 2% to 7%), and malignant epithelial lacrimal gland tumors (9% vs 2% to 3%).

Conclusion.

Our findings highlight the distinctive nature of the orbital oncology experience at a comprehensive cancer center. We found higher than previously reported rates of malignant tumors (63% of all tumors), particularly secondary tumors, malignant epithelial lacrimal gland tumors, and orbital metastases. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Activation of serotonin receptor-2B rescues small-for-size liver graft failure in mice
Authors: Tian Yinghua , Graf Rolf , El-Badry Ashraf Mohammad , Lesurtel Mickaël , Furrer Katarzyna , Moritz Wolfgang , Clavien Pierre-Alain
Published: September 2010

The implantation of grafts below 30% of the normal liver volume is associated with a high risk of failure known as small-for-size (SFS) syndrome. Strategies to rescue small grafts may have a dramatic impact on organ shortage. Serotonin is a potent growth factor for the liver. The goal of this study was to determine whether enhanced serotonin signaling could prevent the deleterious effects of SFS syndrome. We performed 30% normal liver volume transplantations in wild-type C57/BL6 and interleukin-6 (IL-6)−/− mice. Some animals received α-methyl-5-HT (DOI), an agonist of serotonin receptor-2 (5-HT2B). Endpoints included long-term survival, serum and hepatic markers of liver injury and regeneration, assessment of hepatic microcirculation by intravital fluorescence microscopy and scanning electron microscopy, and transcript levels of a variety of serotonin receptors, tumor necrosis factor α, and IL-6. All recipients of small grafts (controls) died within 2-4 days of transplantation, whereas half of those receiving DOI survived permanently. Control animals disclosed major liver injury, including diffuse microvesicular steatosis in hepatocytes, impairment of microcirculation, and a failure of regeneration, whereas these parameters were dramatically improved in animals subjected to DOI. Blockage of 5-HT2B blunted the protective effects of DOI. Whereas IL-6 levels were higher in DOI-treated animals, IL-6−/− mice were still protected by DOI, suggesting a protective pathway independent of IL-6.

Conclusion:

Serotonin through its action on receptor-2B protects SFS liver grafts from injury and prevents microcirculation and regeneration. The mechanism of hepato-protection is independent of IL-6. (Hepatology 2011;)
Novel mechanism by which histone deacetylase inhibitors facilitate topoisomerase IIα degradation in hepatocellular carcinoma cells
Authors: Chen Mei-Chuan , Chen Chun-Han , Chuang Hsiao-Ching , Kulp Samuel K. , Teng Che-Ming , Chen Ching-Shih
Published: September 2010

Histone deacetylase (HDAC) inhibitors exhibit a unique ability to degrade topoisomerase (topo)IIα in hepatocellular carcinoma (HCC) cells, which contrasts with the effect of topoII-targeted drugs on topoIIβ degradation. This selective degradation might foster novel strategies for HCC treatment in light of the correlation of topoIIα overexpression with the aggressive tumor phenotype and chemoresistance. Here we report a novel pathway by which HDAC inhibitors mediate topoIIα proteolysis in HCC cells. Our data indicate that HDAC inhibitors transcriptionally activated casein kinase (CK)2α expression through increased association of acetylated histone H3 with the CK2α gene promoter. In turn, CK2 facilitated the binding of topoIIα to COP9 signalosome subunit (Csn)5 by way of topoIIα phosphorylation. Furthermore, we identified Fbw7, a Csn5-interacting F-box protein, as the E3 ligase that targeted topoIIα for degradation. Moreover, knockdown of CK2α, Csn5, or Fbw7 reversed HDAC inhibitor-induced topoIIα degradation. Mutational analysis indicates that the 1361SPKLSNKE1368 motif plays a crucial role in regulating topoIIα protein stability. This motif contains the consensus recognition sites for CK2 (SXXE), glycogen synthase kinase (GSK)3β (SXXXS), and Fbw7 (SPXXS). This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361. This double phosphorylation facilitated the recruitment of Fbw7 to the phospho-degron 1361pSPKLpS1365 of topoIIα, leading to its ubiquitin-dependent degradation.

Conclusion

: This study shows a novel pathway by which HDAC inhibitors facilitate the selective degradation of topoIIα, which underlies the complexity of the functional role of HDAC in regulating tumorigenesis and aggressive phenotype in HCC cells. (Hepatology 2011;)
Ergonomic planned supply in an automotive assembly line
Authors: Baraldi Emilio C. , Paulo C. Kaminski
Published: September 2010

The objective of this research is to identify the benefits of ergonomic improvements in workstations and in planned parts supply in an automotive assembly line. Another aim is to verify to what extent it is possible to create competitive advantages in the manufacturing area with reduction in vehicle assembly time by using technological investments in ergonomics with benefits to the worker and to the company. The Methods Time Measurement (MTM) methodology is chosen to measure the process time differences. To ensure a reliable comparison, a company in Brazil that has two different types of assembly line installations in the same plant was observed, and both assembly lines were under the same influences in terms of human resources, wages, food, and educational level of the staff. In this article, the first assembly line is called “new” and was built 6 years ago, with high investments in ergonomic solutions, in the supply system, and in the process. The other is called “traditional” and was built 23 years ago with few investments in the area. © 2010 Wiley Periodicals, Inc.
Hippocampal subregions differentially associate with standardized memory tests
Authors: Brickman Adam M. , Stern Yaakov , Small Scott A.
Published: September 2010

Recent studies suggest that individual hippocampal subregions perform distinct cognitive operations and are differentially targeted by aging and disease. Although originally developed to assess global hippocampal function, whether performance on standard memory tests used in neuropsychological batteries is associated with individual hippocampal subregions remains unknown. Here we addressed this issue by imaging 210 neuropsychologically characterized subjects using a high‐resolution variant of functional magnetic resonance imaging that generates maps reflective of basal hippocampal metabolism. Regression analysis revealed memory tests that differentially associate with two hippocampal subregions, the entorhinal cortex (EC) and the dentate gyrus (DG). Whereas performance on the delayed retention component of the Selective Reminding Test was associated with the EC, performance on the recognition component of the Benton Visual Retention Test (BVRT) was associated with the DG. Furthermore, elevation in blood glucose, previously shown to target the DG, was found to correlate selectively with the recognition component of the BVRT. These findings provide further evidence that the hippocampal subregions perform distinct roles, and, interpreted in the context of previous neuropsychological and imaging studies, confirm that aging and Alzheimer's disease target different hippocampal subregions. © 2010 Wiley‐Liss, Inc.
Hierarchical relational binding in the medial temporal lobe: The strong get stronger
Authors: Shimamura Arthur P.
Published: September 2010

Controversy exists over the functional role of the medial temporal lobe (MTL) in episodic memory. Some have suggested that the hippocampus plays a unique and qualitatively different role than other MTL regions, whereas others suggest that the entire MTL has one functional role, which is to support the consolidation of declarative memories. Hierarchical relational binding theory (hRBT) purports that the functional role of the entire MTL is the binding of features associated with an episodic experience. As the hippocampus sits at the top of this hierarchy, binding at this level is particularly efficient in reinstating event features at the time of retrieval. Thus, this theory offers a unified account of MTL that yields outcomes similar to theories that suggest a special role of the hippocampus. In this way, hRBT captures features of both single‐ and dual‐process models of MTL and reconciles controversies about the nature of episodic recollection. © 2010 Wiley‐Liss, Inc.
Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute lymphoblastic leukaemia in Javanese children
Authors: Chan Jason Yong‐Sheng , Ugrasena Dewa G , Lum Danny Wai‐Kiong , Lu Yi , Yeoh Allen Eng‐Juh
Published: September 2010

Xenobiotic and folate metabolic pathways are important for the maintenance of genetic stability and may influence susceptibility to the development of childhood acute lymphoblastic leukaemia (ALL). In this study, we investigated 10 polymorphisms in 6 genes (GSTM1‐present/null, GSTT1‐present/null, GSTP1 1578A > G, NQO1 609C > T, MTHFR 677C > T, MTHFR 1298A > C, MTHFD1 1958G > A, 3′‐TYMS 1494 6bp‐deletion/insertion, 5′‐TYMS 28bp‐tandem repeats, and SLC19A1 80G > A) in a cohort of 185 Javanese children with ALL and 177 healthy controls. In ALL patients, none of the polymorphisms demonstrated a statistically significant association with ALL after correcting for multiple comparisons. Gender‐stratified analysis showed that in girls, GSTT1‐null genotype was associated with increased ALL risk (OR = 2.20; p = 0.027), while GSTP1 1578AG genotype was associated with reduced risk (OR = 0.43; p = 0.031). Strong linkage disequilibrium between the MTHFR 677C > T and 1298A > C polymorphisms was observed (D′ = 1.0; r2 = 0.072). The haplotypes 677C‐1298C and 677T‐1298A were associated with a reduced risk of ALL (OR = 0.68 and 0.64, respectively; gender‐adjusted global p = 0.028). Classification and regression tree (CART) analysis was employed to identify potential high‐order gene‐gene interactions and cluster subjects into susceptibility groups. SLC19A1 80G > A emerged as the predominant polymorphism associated with risk of ALL. Individuals simultaneously carrying MTHFR 1298AA, 3'‐TYMS 6bp deletion(s) and SLC19A1 80A‐allele(s) were at higher disease risk (OR = 2.21; p < 0.001). On the contrary, simultaneous possession of MTHFR 1298CC, 3'‐TYMS 6bp homozygosity and SLC19A1 80A‐allele(s) conferred lower risk (OR = 0.25; p = 0.004). Carriage of NQO1 609C‐allele amongst SLC19A1 80GG genotype was associated with lower risk (OR = 0.47; p = 0.003). In conclusion, our study has demonstrated the importance of gender and gene‐gene interaction within the xenobiotic and folate pathways in modulating childhood ALL susceptibility. Copyright © 2010 John Wiley & Sons, Ltd.
Thermodynamic consistency of potential evapotranspiration estimates in Florida
Authors: Chin David A.
Published: September 2010

This study investigates the validity of fundamental assumptions regarding the partitioning of energy that are implicit in the Penman–Monteith (PM) and Priestly–Taylor (PT) models of potential evapotranspiration (PET). Both these models require energy conservation, but differ in the partitioning of sensible and latent heat fluxes as measured by the Bowen ratio. Application of these models at four research sites in Florida collectively show that these models can be calibrated to provide adequate PET prediction at all sites. The prediction of Bowen ratios using the calibrated PET models showed that the PT model is preferable for lakes and is acceptable for marsh and forest; the crop‐coefficient application of the PM model is preferable for grass and is acceptable for marsh; and the standard PM model is acceptable for marsh. For the marsh and forest covers, the margins of preference between the three models are not very strong. This investigation was limited to climatic conditions in Florida and caution should be exercised in extending these results to other sites and climates. Copyright © 2010 John Wiley & Sons, Ltd.
Stream temperature dynamics in two hydrogeomorphically distinct reaches
Authors: Leach J. A. , Moore R. D.
Published: September 2010

The objective of this study was to analyse stream temperature variability during summer in relation to both surface heat exchanges and reach‐scale hydrology for two hydrogeomorphically distinct reaches. The study focused on a 1·5‐km wildfire‐disturbed reach of Fishtrap Creek located north of Kamloops, British Columbia. Streamflow measurements and longitudinal surveys of electrical conductivity and water chemistry indicated that the upper 750 m of the study reach was dominated by flow losses. A spring discharged into the stream at 750 m below the upper reach boundary. Below the spring, the stream was neutral to losing on three measurement days, but gained flow on a fourth day that followed a rain event. Continuous stream temperature measurements typically revealed a downstream warming along the upper 750 m of the study reach on summer days, followed by a pronounced cooling associated with the spring, with little downstream change below the spring. Modelled surface energy exchanges were similar over the upper and lower sub‐reaches, and thus cannot explain the differences in longitudinal temperature patterns. Application of a Lagrangian stream temperature model provided reasonably accurate predictions for the upper sub‐reach. For the lower sub‐reach, accurate prediction required specification of concurrent flow losses and gains as a hydrological boundary condition. These findings are consistent with differences in the hydrogeomorphology of the upper and lower sub‐reaches. The modelling exercise indicated that substantial errors in predicted stream temperature can occur by representing stream‐surface exchange as a reach‐averaged one‐directional flux computed from differences in streamflow between the upper and lower reach boundaries. Further research should focus on reliable methods for quantifying spatial variations in reach‐scale hydrology. Copyright © 2010 John Wiley & Sons, Ltd.
Improvement of distributed snowmelt energy balance modeling with MODIS‐based NDSI‐derived fractional snow‐covered area data
Authors: Homan Joel W. , Luce Charles H. , McNamara James P. , Glenn Nancy F.
Published: September 2010

Describing the spatial variability of heterogeneous snowpacks at a watershed or mountain‐front scale is important for improvements in large‐scale snowmelt modelling. Snowmelt depletion curves, which relate fractional decreases in snow‐covered area (SCA) against normalized decreases in snow water equivalent (SWE), are a common approach to scale‐up snowmelt models. Unfortunately, the kinds of ground‐based observations that are used to develop depletion curves are expensive to gather and impractical for large areas. We describe an approach incorporating remotely sensed fractional SCA (FSCA) data with coinciding daily snowmelt SWE outputs during ablation to quantify the shape of a depletion curve. We joined melt estimates from the Utah Energy Balance Snow Accumulation and Melt Model (UEB) with FSCA data calculated from a normalized difference snow index snow algorithm using NASA's moderate resolution imaging spectroradiometer (MODIS) visible (0·545–0·565 µm) and shortwave infrared (1·628–1·652 µm) reflectance data. We tested the approach at three 500 m2 study sites, one in central Idaho and the other two on the North Slope in the Alaskan arctic. The UEB‐MODIS‐derived depletion curves were evaluated against depletion curves derived from ground‐based snow surveys. Comparisons showed strong agreement between the independent estimates. Copyright © 2010 John Wiley & Sons, Ltd.
PRKAR1A is overexpressed and represents a possible therapeutic target in human cholangiocarcinoma
Authors: Loilome Watcharin , Juntana Sirinun , Namwat Nisana , Bhudhisawasdi Vajarabhongsa , Puapairoj Anucha , Sripa Banchob , Miwa Masanao , Saya Hideyuki , Riggins Gregory J. , Yongvanit Puangrat
Published: September 2010

The protein kinase A regulatory subunit 1 alpha (PRKAR1A/PKAI) pathway is overexpressed in varieties of tumors and cancer cell lines including cholangiocarcinoma (CCA), although its role in CCA growth modulation is unclear. In our study, we evaluated the effect of PRKAR1A/PKAI targeting on CCA cell proliferation. Real‐time PCR demonstrated an increased mRNA expression of PRKAR1A/PKAI, whereas protein kinase A regulatory subunit 2 beta (PRKAR2B/PKAII) was downregulated in human CCA tissues and CCA cell lines. Immunohistochemistry of human CCA tissues revealed increased PRKAR1A with decreased PRKAR2B protein expression. Moreover, CCA cell lines showed abundantly expressed PRKAR1A, while lacking PRKAR2B expression. Silencing PRKAR1A expression induced growth inhibition and apoptosis of CCA cells, with an associated decrease in mitogen‐activated protein kinases, PI3K/Akt, JAK/STAT and Wnt/β‐catenin pathway signaling. The inhibition of PKA using a PKA inhibitor and cAMP analogs also led to a significant cell growth inhibition. In conclusion, our study reports the overexpression as well as molecular mechanisms by which PRKAR1A/PKA regulates human CCA cell growth. Importantly, abrogation of gene expression caused significant CCA cell growth inhibition, oncogenic signaling and coupled apoptosis induction, suggesting PRKAR1A's potential as a drug target for CCA therapy.
Forced expression of Sox21 inhibits Sox2 and induces apoptosis in human glioma cells
Authors: Ferletta Maria , Caglayan Demet , Mokvist Liza , Jiang Yiwen , Kastemar Marianne , Uhrbom Lene , Westermark Bengt
Published: September 2010

Numerous studies support a role for Sox2 to keep stem cells and progenitor cells in an immature and proliferative state. Coexpression of Sox2 and GFAP has been found in regions of the adult brain where neural stem cells are present and in human glioma cells. In our study, we have investigated the roles of Sox2 and its counteracting partner Sox21 in human glioma cells. We show for the first time that Sox21 is expressed in both primary glioblastoma and in human glioma cell lines. We found that coexpression of Sox2, GFAP and Sox21 was mutually exclusive with expression of fibronectin. Our result suggests that glioma consists of at least two different cell populations: Sox2+/GFAP+/Sox21+/FN− and Sox2−/GFAP−/Sox21−/FN+. Reduction of Sox2 expression by using siRNA against Sox2 or by overexpressing Sox21 using a tetracycline‐regulated expression system (Tet‐on) caused decreased GFAP expression and a reduction in cell number due to induction of apoptosis. We suggest that Sox21 can negatively regulate Sox2 in glioma. Our findings imply that Sox2 and Sox21 may be interesting targets for the development of novel glioma therapy.
Randomized healthservices study of human papillomavirus‐based management of low‐grade cytological abnormalities
Authors: Dillner Lena , Kemetli Levent , Elfgren Kristina , Bogdanovic Gordana , Andersson Pia , Carlsten‐Thor Agneta , Andersson Sonia , Persson Elisabeth , Rylander Eva , Grillner Lena , Dillner Joakim , Törnberg Sven
Published: September 2010

Human papillomavirus (HPV)‐based management of women with borderline atypical squamous cells of undetermined significance (ASCUS) or mildly abnormal cervical intraepithelial neoplasia (CINI) cervical cytology has been extensively studied in the research setting. We wished to assess safety and health care resource use of a real‐life health care policy using HPV triaging. All 15 outpatient clinics involved in the organized population‐based screening program in Stockholm, Sweden screening program were randomized to either continue with prior policy (colposcopy of all women with ASCUS/CINI) or to implement a policy with HPV triaging and colposcopy only of HPV‐positive women. The trial enrolled the 3,319 women who were diagnosed with ASCUS (n = 1,335) or CINI (n = 1,984) in Stockholm during 17th March 2003 to 16th January 2006. Detection of high‐grade cervical lesions (CINII+) and health care cost consumption was studied by registry linkages. The proportion of histopathology‐verified CINII+ was similar for the two policies (395 of 1,752 women (22.5%; 95% Confidence interval [CI]: 20.6–24.6%) had CINII+ diagnosed with HPV triaging policy, 318 of 1,567 women (20.3%; 95%CI: 18.3–22.4%) had CINII+ with colposcopy policy). Sixty‐four percent of women with ASCUS and 77% of women with CINI were HPV positive. HPV‐positivity was age‐dependent, with 81% of women below 35 years of age and 44% of women above 45 years of age testing HPV‐positive. HPV triaging was cost‐effective only above 35 years of age. In conclusion, a real‐life randomized healthservices study of HPV triaging of women with ASCUS/CINI demonstrated similar detection of CINII+ as colposcopy of all women.
Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH‐AARP Diet and Health Study
Authors: Kilfoy Briseis A. , Zhang Yawei , Park Yikyung , Holford Theodore R. , Schatzkin Arthur , Hollenbeck Albert , Ward Mary H.
Published: September 2010

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health‐American Association of Retired Persons (NIH‐AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50–71 years in 1995–1996. Dietary intakes were assessed using a 124‐item food frequency questionnaire. During an average of 7 years of follow‐up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29–4.041; p‐trend <0.001); however, we observed no trend with intake among women (p‐trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09–4.05; p‐trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03–11.4; p‐trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86–8.77; p‐trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted.
High constant incidence rates of second primary cancers of the head and neck: A pooled analysis of 13 cancer registries
Authors: Bosetti Cristina , Scelo Ghislaine , Chuang Shu‐Chun , Tonita Jon M. , Tamaro Sharon , Jonasson Jon G. , Kliewer Erich V. , Hemminki Kari , Weiderpass Elisabete , Pukkala Eero , Tracey Elizabeth , Olsen Jorgen H. , Pompe‐Kirn Vera , Brewster David H. , Martos Carmen , Chia Kee‐Seng , Brennan Paul , Hashibe Mia , Levi Fabio , La Vecchia Carlo , Boffetta Paolo
Published: September 2010

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population‐based cancer registries from Europe, Canada, Australia and Singapore for the years 1943–2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person‐years of follow‐up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30–34 to 46.2/100,000 at age 70–74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30–34 to 16.5/100,000 at age 80–84. However, age‐specific incidence of second HN cancers after a first HN cancer in men was around 200–300/100,000 between age 40–44 and age 70–74 and tended to decline at subsequent ages (150/100,000 at age 80–84); in women, incidence of second HN cancers was around 200–300/100,000 between age 45–49 and 80–84. The patterns of age‐specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age‐specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.
Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper
Authors: Duffy Michael J. , van Rossum Leo G. M. , van Turenhout Sietze T. , Malminiemi Outi , Sturgeon Catherine , Lamerz Rolf , Nicolini Andrea , Haglund Caj , Holubec Lubos , Fraser Callum G. , Halloran Stephen P.
Published: September 2010

Several randomized controlled trials have shown that population‐based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high‐risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population‐based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic‐based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis.
Farnesyl transferase inhibitor treatment of breast cancer cells leads to altered RhoA and RhoC GTPase activity and induces a dormant phenotype
Authors: Chatterjee Moumita , van Golen Kenneth L.
Published: September 2010

Farnesyl transferase inhibitors (FTIs) were shown to be effective in modulating tumor growth in Ras‐transformed tumor cells. Recent studies have focused on Rho GTPases as putative targets of FTI action. Previously, we demonstrated that FTIs were effective in inhibiting the growth and invasiveness of RhoC GTPase‐overexpressing inflammatory breast cancer (IBC) cells however, RhoC activity was increased. In this study, we examine the mechanisms of FTI action on breast cancer cells in culture through modulation of RhoC and RhoA GTPases. We found that FTI inhibition of breast cancer cell growth was reversible and resembled what has been described for an in vitro model of tumor cell dormancy. On FTI treatment, levels of active RhoA decreased significantly, whereas levels of active RhoC increased 3.8‐fold. We studied the role of these two GTPases in a fibronectin and basic FGF‐induced model of breast cancer cell dormancy. Hypoactivation of RhoA and hyperactivation of RhoC were seen to induce morphology and growth changes consistent with tumor cell dormancy in culture. In addition, the JNK/SAPK pathway was induced on FTI treatment. A pharmacologic inhibitor of the JNK/SAPK pathway significantly reduced the number of dormant cells. This study has implications for the use of FTIs as therapeutic agents as well as potential mechanisms for breast cancer cell dormancy.
Curcumin decreases cholangiocarcinogenesis in hamsters by suppressing inflammation‐mediated molecular events related to multistep carcinogenesis
Authors: Prakobwong Suksanti , Khoontawad Jarinya , Yongvanit Puangrat , Pairojkul Chawalit , Hiraku Yusuke , Sithithaworn Paiboon , Pinlaor Porntip , Aggarwal Bharat B. , Pinlaor Somchai
Published: September 2010

Cholangiocarcinoma (CCA) is a highly metastatic tumor linked to liver fluke infection and consumption of nitrosamine‐contaminated foods and is a major health problem especially in South‐Eastern Asia. In search for a suitable chemopreventive agents, we investigated the effect of curcumin, a traditional anti‐inflammatory agent derived from turmeric (Curcuma longa), on CCA development in an animal model by infection with the liver fluke Opisthorchis viverrini and administration of N‐nitrosodimethylamine and fed with curcumin‐supplemented diet. The effect of curcumin‐supplemented diet on histopathological changes and survival were assessed in relation to NF‐κB activation, and the expression of NF‐κB‐related gene products involved in inflammation, DNA damage, apoptosis, cell proliferation, angiogenesis and metastasis. Our results showed that dietary administration of this nutraceutical significantly reduced the incidence of CCA and increased the survival of animals. This correlated with the suppression of the activation of transcription factors including NF‐κB, AP‐1 and STAT‐3, and reduction in the expression of proinflammatory proteins such as COX‐2 and iNOS. The formation of iNOS‐dependent DNA lesions (8‐nitroguanine and 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine) was inhibited. Curcumin suppressed the expression of proteins related to cell survival (bcl‐2 and bcl‐xL), proliferation (cyclin D1 and c‐myc), tumor invasion (MMP‐9 and ICAM‐1) and angiogenesis (VEGF), and microvessel density. Induction of apoptotic events as indicated by caspase activation and PARP cleavage was also noted. Our results suggest that curcumin exhibits an anticarcinogenic potential via suppression of various events involved in multiple steps of carcinogenesis, which is accounted for by its ability to suppress proinflammatory pathways.
Manuscript size limitations
Authors: Hodgson Ernest
Published: September 2010

© 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:217, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20363
Does the Agulhas Current amplify global temperatures during super‐interglacials?
Authors: Turney Chris S.M. , Jones Richard T.
Published: September 2010

Future projections of climate suggest our planet is moving into a ‘super‐interglacial’. Here we report a global synthesis of ice, marine and terrestrial data from a recent palaeoclimate equivalent, the Last Interglacial (ca. 130–116 ka ago). Our analysis suggests global temperatures were on average ∼1.5°C higher than today (relative to the AD 1961–1990 period). Intriguingly, we identify several Indian Ocean Last Interglacial sequences that suggest persistent early warming, consistent with leakage of warm, saline waters from the Agulhas Current into the Atlantic, intensifying meridional ocean circulation and increasing global temperatures. This mechanism may have played a significant positive feedback role during super‐interglacials and could become increasingly important in the future. These results provide an important insight into a future 2°C climate stabilisation scenario. Copyright © 2010 John Wiley & Sons, Ltd.
Changing limits and opportunities in globalized financial markets: an overview
Authors: Potter Jonathan
Published: September 2010

This volume explores how entrepreneurial firms and universities can apply strategic change to improve their financial structures and access under‐exploited sources of financial resources.
A novel herbicide‐inducible male sterility system
Authors: Zhang Jinhui , Zhang Wenlu , Yen Yang , Long Hai , Deng Guangbing , Pan Zhifen , Yu Maoqun
Published: September 2010

BACKGROUND: Heterosis is a phenomenon that first‐generation offspring perform better than their parents. Conventional breeding methods have their shortcomings. It would be optimal to construct inducible male sterile plants.

RESULTS: We developed a novel system for creating male sterile transgenic plants by downregulating the specific expression of the glyphosate tolerance CP4 EPSPS gene in male reproductive tissues. Transcriptional repression was achieved by manipulating DNA binding proteins with their specific corresponding sites. We transferred the CP4 EPSPS gene driven by a modified CaMV 35S promoter with three tetracycline operator copies in the vicinity of the TATA box and tetracycline repressor gene under the control of an anther‐specific promoter Osg6B to Arabidopsis thaliana. As a result, we successfully obtained controllable transgenic plants: the whole plant could tolerate exposure of glyphosate but the male tissue was sensitive.

CONCLUSION: The novel inducible male sterility system is applied and easy to handle, so it might be applicable to a wide range of crop plants. Copyright © 2010 Society of Chemical Industry
Estimation of chromatographic lipophilicity of bile acids and their derivatives by reversed‐phase thin layer chromatography
Authors: Onişor Cristina , Poša Mihalj , Kevrešan Slavko , Kuhajda Ksenija , Sârbu Costel
Published: September 2010

The main goal of this study was to estimate the lipophilicity and investigate the molecular mechanism of retention of bile acids and their derivatives in order to find an objective manner of quantitative comparison of different chemically bonded stationary phases for high performance TLC in terms of their (dis)similarities. Highly significant correlations were obtained between different experimental indices of lipophilicity (RM0, S and the scores corresponding to the first principal component) estimated on CNF254s and RP‐18F254s and some computed log P values that combine electronic and topological aspects. The most statistically significant quantitative structure–property relationship models, using descriptors from Dragon software, multiple linear regression and genetic algorithm, were also obtained in the case of CNF254s and RP‐18F254s stationary phases. Cross‐validation suggests a good reliability of the results. The contribution of 2D and 3D descriptors, which are related to atomic mass, together with reactivity parameters such as polarizability and electronegativity seem to control the chromatographic mechanism (lipophilicity) on all stationary phases.
Triamine‐bonded stationary phase for open tubular capillary electrochromatography
Authors: Zhang Xiaowei , Lin Xucong , Chen Zhenbin , Wang Xiaochun , Wu Xiaoping , Xie Zenghong
Published: September 2010

A multi‐functional separation column modified with 3‐[2‐(2‐aminoethylamino)ethylamino] propyl‐trimethoxysilane was developed for open tubular capillary electrochromatography. This functional hydrophilic triamine‐bonded open tubular column could generate both anodic and cathodic EOF. When the pH of the running buffer was below 5.3 (30% 3‐[2‐(2‐aminoethylamino)ethylamino] propyl‐trimethoxysilane, v/v), the anodic EOF was exhibited, which greatly prevented the undesired adsorptions of basic proteins on the capillary inner wall. Favorable separation of four basic proteins (viz. trypsin, ribonuclease A, lysozyme and cytochrome c) was successfully achieved at pH 3.5 of 10 mmol/L phosphate buffer. The column efficiencies of proteins were in the range from 87 000 to 110 000 plates/m, and the RSD values for migration time of four proteins were less than 1.2% (run‐to‐run, n=5). The ionic analytes were also separated efficiently in the co‐electroosmotic mode. The average efficiencies ranged from 81 000 to 190 000 plates/m for seven aromatic acids and 186 000–245 000 plates/m for four nucleoside monophosphates, respectively, and good capillary column repeatability was gained with RSD of the migration time not more than 3.0%. The triamine‐bonded open tubular capillary column is favorable to be an alternative functional medium for the further analysis of basic proteins and anionic analytes.
The effect of mouth breathing versus nasal breathing on dentofacial and craniofacial development in orthodontic patients
Authors: Harari Doron , Redlich Meir , Miri Shalish , Hamud Tachsin , Gross Menachem
Published: September 2010

Objectives/Hypothesis:

To determine the effect of mouth breathing during childhood on craniofacial and dentofacial development compared to nasal breathing in malocclusion patients treated in the orthodontic clinic.

Study Design:

Retrospective study in a tertiary medical center.

Methods:

Clinical variables and cephalometric parameters of 116 pediatric patients who had undergone orthodontic treatment were reviewed. The study group included 55 pediatric patients who suffered from symptoms and signs of nasal obstruction, and the control group included 61 patients who were normal nasal breathers.

Results:

Mouth breathers demonstrated considerable backward and downward rotation of the mandible, increased overjet, increase in the mandible plane angle, a higher palatal plane, and narrowing of both upper and lower arches at the level of canines and first molars compared to the nasal breathers group. The prevalence of a posterior cross bite was significantly more frequent in the mouth breathers group (49%) than nose breathers (26%), (P = .006). Abnormal lip‐to‐tongue anterior oral seal was significantly more frequent in the mouth breathers group (56%) than in the nose breathers group (30%) (P = .05).

Conclusions:

Naso‐respiratory obstruction with mouth breathing during critical growth periods in children has a higher tendency for clockwise rotation of the growing mandible, with a disproportionate increase in anterior lower vertical face height and decreased posterior facial height. Laryngoscope, 2010
Meta‐analysis for the effect of medical therapy vs. Placebo on recovery of idiopathic sudden hearing loss
Authors: Labus Jakob , Breil Judith , Stützer Hartmut , Michel Olaf
Published: September 2010

Objectives:

To estimate the effect of recovery of idiopathic sudden hearing loss under placebo (first aim) and under medical therapy (second aim).

Study Design:

Systematic review and meta‐analysis.

Methods:

A total of 1,674 studies published between January 1974 and April 2009 were found following suggestions in the Cochrane Handbook for Systematic Reviews. After filtering by criteria of Cochrane Collaboration, four trials remained for continuous and two for dichotomous data.

Results:

Using Review Manager, weighted mean difference as well as standardized mean effect of hearing recovery were calculated and pooled. The values for weighted mean difference of hearing gain in dB were 0.79, 95% confidence interval (CI) (−2.04–3.61) and for standardized mean effect 0.06, 95% CI (−0.13–0.24), respectively, which computationally favors active treatment, but statistically is not significantly different from no effect (0 dB). This was in accordance to the comparison of descriptive means between recovery under placebo with 14.3 dB and active treatment with 15.8 dB hearing gain. Treatment effect of dichotomous data (hearing gain vs. no hearing gain) suggested a statistically significant better outcome for active treatment; the odds ratio (OR) [fixed] is 2.18 (1.06–4.46).

Conclusions:

In five different statistical analysis methods used, treatment effect of medical therapy was slightly better than recovery under placebo in which spontaneous recovery could be assumed, but no significant effect was detected. Against the background of recovery under placebo of 14.3 dB vs. 15.8 dB hearing gain of active treatment as averages of all measured frequencies, recovery under placebo seems not to have worse outcome than recovery under medical therapy. Laryngoscope, 2010
Optical coherence tomography allows for the reliable identification of laryngeal epithelial dysplasia and for precise biopsy: A clinicopathological study of 61 patients undergoing microlaryngoscopy
Authors: Just Tino , Lankenau Eva , Prall Friedrich , Hüttmann Gereon , Pau Hans Wilhelm , Sommer Konrad
Published: September 2010

Objectives/Hypothesis:

A newly developed microscope‐based spectral‐domain optical coherence tomography (SD‐OCT) device and an endoscope‐based time‐domain OCT (TD‐OCT) were used to assess the inter‐rater reliability, sensitivity, specificity, and accuracy of benign and dysplastic laryngeal epithelial lesions.

Study Design:

Prospective study.

Methods:

OCT during microlaryngoscopy was done on 35 patients with an endoscope‐based TD‐OCT, and on 26 patients by an SD‐OCT system integrated into an operating microscope. Biopsies were taken from microscopically suspicious lesions allowing comparative study of OCT images and histology.

Results:

Thickness of the epithelium was seen to be the main criterion for degree of dysplasia. The inter‐rater reliability for two observers was found to be kappa = 0.74 (P <.001) for OCT. OCT provided test outcomes for differentiation between benign laryngeal lesions and dysplasia/CIS with sensitivity of 88%, specificity of 89%, PPV of 85%, NPV of 91%, and predictive accuracy of 88%. However, because of the limited penetration depth of the laser light primarily in hyperkeratotic lesions (thickness above 1.5 mm), the basal cell layer was no longer visible, precluding reliable assessment of such lesions.

Conclusions:

OCT allows for a fairly accurate assessment of benign and dysplastic laryngeal epithelial lesion and greatly facilitates the taking of precise biopsies. Laryngoscope, 2010
Gentamicin alters nitric oxide production in semicircular canals and otolith organs
Authors: Helling Kai , Heinrich Ulf‐Rüdiger , Heusgen Lukas , Brieger Jürgen , Schmidtmann Irene , Li Huige , Mann Wolf J.
Published: September 2010

Objectives/Hypothesis:

Intratympanic application of gentamicin is an important therapeutic option to control vertigo spells in Ménière's disease. Low doses eliminate the function of semicircular canal ampullae (SCCA) and saccule in most patients, although utricular function is maintained in many cases. Local alteration in free radical production might be responsible for these differences. Therefore, the gentamicin‐induced nitric oxide (NO) production was determined in an animal model using separate organ cultures of SCCA, saccule, and utricle.

Study Design:

Prospective pilot study in male guinea pigs.

Methods:

SCCA, saccule, and utricle of 28 guinea pigs were isolated and incubated separately for 6 hours in cell culture medium. Gentamicin was administered in two different concentrations (0.4 mg/mL and 0.8 mg/mL) to organ cultures of 16 animals. Tissues from 12 animals were used as controls. Nitric oxide was quantified by chemiluminescence.

Results:

Gentamicin led to an NO increase of about 70% in the saccule, an NO reduction of more than 70% in SCCA, and an NO reduction of 36% in the utricle.

Conclusions:

The selective effects of gentamicin on the NO production in the different sensory areas of the vestibular organ have to be taken into account in the therapy of Ménière's disease. Laryngoscope, 2010
Management of giant sialoliths: Review of the literature and preliminary experience with interventional sialendoscopy
Authors: Wallace Eric , Tauzin Marcie , Hagan Joseph , Schaitkin Barry , Walvekar Rohan R.
Published: September 2010

Objectives/Hypothesis:

To report our experience with management of giant salivary stones via a combined approach technique using salivary endoscopy (CA) and results of a review of current literature related to giant salivary stones.

Study Design:

Retrospective case series.

Methods:

An institutional review board‐approved chart review was performed on patients managed with a CA to treat giant salivary stones (≥15 mm). In addition, we reviewed the English literature from 1942 to 2009.

Results:

Table 1 consists of 54 stones; 47 of which were identified during the review of literature and 7 from our case series. Of those 47 stones, 23 were hilar in location, 23 were glandular in location, and 1 stone was missing data. The gland preservation rate in the 47 reported stones was 57% (17/30). Among patients where gland resection was reported, the majority of the patients (12/13) had hilar glandular stones. Only one patient with a ductal stone had a gland resection. In our series, CA enabled a gland preservation rate of 86% (6/7). Among these patients, stone location was hilar glandular in six (86%) and ductal in one (14%). The mean size of stones from the literature review was 35 mm and from our series was 19 mm.

Conclusions:

Our review reflects current treatment recommendations for giant stones, i.e., transoral sialolithotomy for ductal stones and gland resection for hilar glandular stones. Our preliminary experience with CA for giant stones suggests improved gland preservation rates (86% vs. 57%) independent of stone location and with preservation of salivary function. Laryngoscope, 2010