bluuebunny/crossref_metadata_2025 huggingface dataset:
Cationic Rhodium(I)/Modified‐BINAP Catalyzed [2 + 2 + 2] Cycloaddition of Alkynes with Nitriles.
Authors: Tanaka Ken , Suzuki Nanami , Nishida Goushi
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Novel Potent and Selective αvβ3/αvβ5 Integrin Dual Antagonists with Reduced Binding Affinity for Human Serum Albumin.
Authors: Raboisson Pierre , Manthey Carl L. , Chaikin Margery , Lattanze Jennifer , Crysler Carl , Leonard Kristi , Pan Wenxi , Tomczuk Bruce E. , Marugan Juan Jose
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and Cross‐Coupling Reactions of 7‐Azaindoles via a New Donor—Acceptor Cyclopropane.
Authors: Zheng Xiaomei , Kerr Michael A.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Novel Conversion of Acetylenic 1,2,4‐Triazoles into 3‐Alkyl‐5‐arylpyridazines.
Authors: Crowley Patrick J. , Russell Sally E. , Reynolds Laurence G.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Oxidation of Hydroxyl‐Substituted Organotrifluoroborates.
Authors: Molander Gary A. , Petrillo Daniel E.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
2‐Arylazo‐1‐vinylpyrroles: A Novel Promising Family of Reactive Dyes.
Authors: Trofimov Boris A. , et al. et al.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and in vitro Antibacterial Activity of Novel Heterocyclic Derivatives of 18‐nor‐Equilenin.
Authors: Karnik A. V. , Malviya N. J. , Kulkarni A. M. , Jadhav B. L.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
First Total Synthesis of Louisianin A (I).
Authors: Chang Ching‐Yao , Liu Hui‐Ming , Chow Tahsin J.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Nonsymmetrical Five‐Ring Achiral Banana‐Shaped Liquid Crystals Comprising Salicylaldimine Mesogenic Segment
Authors: Yelamaggad Channabasaveshwar V. , Shashikala Indudhara Swamy , Nair Geetha G. , Rao Doddamane S. Shankar , Prasad Subbarao Krishna
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Design, Synthesis, and Biochemical Evaluation of Novel Cruzain Inhibitors with Potential Application in the Treatment of Chagas′ Disease.
Authors: Siles Rogelio , Chen Shen‐En , Zhou Ming , Pinney Kevin G. , Trawick Mary Lynn
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Chemical Vapour Deposition Methods for Protection Against Wear
Authors: Wheeler D. W.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Physical Properties of Nano‐Manganites and Carbon Nanotubes
Authors: Dhami Amarjot Kaur
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Metallacycloalkenes — Synthesis, Structure and Reactivity of Medium to Large Ring Compounds
Authors: Blom Burget , Clayton Hadley , Kilkenny Mairi , Moss John R.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Polyvalent Iodine in Organic Chemistry: Recent Developments, 2002—2005
Authors: Matveeva E. D. , Proskurnina M. V. , Zefirov N. S.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Peptide Conjugates of Oligonucleotides: Synthesis and Applications
Authors: Venkatesan Natarajan , Kim Byeang Hyean
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Excitons in Conjugated Oligomer Aggregates, Films, and Crystals
Authors: Spano Frank C.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Theoretical Studies on the Ring Opening of β‐Lactams: Processes in Solution and in Enzymatic Media
Authors: Lopez R. , Menendez M. I. , Diaz N. , Suarez D. , Campomanes P. , Ardura D. , Sordo T. L.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Extended safety and efficacy data on S‐1 plus cisplatin in patients with untreated, advanced gastric carcinoma in a multicenter phase II study
Authors: Lenz Heinz‐Joseph , Lee Fa‐Chyi , Haller Daniel G. , Singh Deepti , Benson Al B. , Strumberg Dirk , Yanagihara Ronald , Yao James C. , Phan Alexandra T. , Ajani Jaffer A.
Published: November 2006

BACKGROUND.

S‐1 is a promising oral fluoropyrimidine. The authors obtained extended Phase II safety and efficacy data in a multicenter setting for the S‐1 plus cisplatin combination: The experimental arm of the global Phase III First‐Line Advanced Gastric Cancer Study (FLAGS) is being compared with 5‐fluorouracil/cisplatin.

METHODS.

Eligible patients had untreated, histologically confirmed advanced gastric cancer (AGC), a Karnofsky performance status (KPS) ≥70%, adequate organ function, and provided written consent. Patients received S‐1 (25 mg/m2 twice daily on Days 1 through 21) plus cisplatin (75 mg/m2 on Day 1) every 28 days. The confirmed overall response rate (CORR) also was designated by an external review. The time to progression (TTP), median survival (MS), and safety were assessed.

RESULTS.

All 72 patients were assessed for safety and survival, and 64 patients were assessed for CORR. The median KPS was 90%. The median number of treatment cycles was 4. The CORR was 55% (95% confidence interval [95% CI], 42–67%). The median duration of response was >5 months. At 6 months, only an estimated 38% of patients had cancer progression. The estimated MS was 10.4 months (95% CI, 8.6–12.9 months). At least 1 serious adverse event occurred in 44% of patients. The frequent grade 3 or 4 toxicities (using the National Cancer Institute Common Toxicity Criteria), which occurred in >10% of patients, included fatigue/asthenia (24%), emesis (17%), nausea (15%), diarrhea (13%), and neutropenia (19%). Complicated neutropenia (1.4%) and grade 4 diarrhea (1.4%) were rare.

CONCLUSIONS.

The current extended data confirmed that S‐1 combined with cisplatin had a highly desirable safety profile. The efficacy against AGC, according to an external review, was encouraging. FLAGS is expected to complete its accrual of 1050 patients by December 2007. Cancer 2007. © 2006 American Cancer Society.
Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy
Authors: Inagaki Masatoshi , Yoshikawa Eisho , Matsuoka Yutaka , Sugawara Yuriko , Nakano Tomohito , Akechi Tatsuo , Wada Noriaki , Imoto Shigeru , Murakami Koji , Uchitomi Yosuke ,   and The Breast Cancer Survivors' Brain MRI Database Group
Published: November 2006

BACKGROUND.

Previous studies have shown cognitive impairment in breast cancer survivors who were exposed to adjuvant chemotherapy. Neural damage by chemotherapy might have played some part in these findings. The current study explored the regional brain volume difference between breast cancer survivors exposed to adjuvant chemotherapy (C+) and those unexposed (C−).

METHODS.

High‐resolution 1.5‐tesla brain magnetic resonance imaging (MRI) databases of breast cancer survivors and healthy controls were used. Brain images were preprocessed for optimal voxel‐based morphometry. Comparisons of gray matter and white matter were performed between the C+ and the C− groups, by using MRI scans from within 1 year (the 1‐year study, n = 51 and n = 55, respectively) or 3 years after their cancer surgery (the 3‐year study, n = 73 and n = 59, respectively). As exploratory analyses, correlation analyses were performed between indices of the Wechsler Memory Scale‐Revised and regional brain volume where the volume were significantly smaller. As a reference, MRI scans of cancer survivors were compared with those of healthy controls (n = 55 for the 1‐year study and n = 37 for the 3‐year study).

RESULTS.

The C+ patients had smaller gray matter and white matter including prefrontal, parahippocampal, and cingulate gyrus, and precuneus in the 1‐year study. However, no difference was observed in the 3‐year study. The volumes of the prefrontal, parahippocampal gyrus, and precuneus were significantly correlated with indices of attention/concentration and/or visual memory. Comparisons with healthy controls did not show any significant differences.

CONCLUSIONS.

Adjuvant chemotherapy might have an influence on brain structure, which may account for previously observed cognitive impairments. Cancer 2007. © 2006 American Cancer Society.
Second solid cancers after allogeneic hematopoietic stem cell transplantation
Authors: Gallagher Genevieve , Forrest Donna L.
Published: November 2006

BACKGROUND.

The objective of this study was to establish the incidence and risk factors for the development of second solid cancers after allogeneic hematopoietic stem cell transplantation (allo‐HSCT).

METHODS.

The authors reviewed the case files of 926 consecutive patients who underwent allo‐HSCT at their institution between 1985 and 2003.

RESULTS.

Twenty‐eight patients developed 30 solid malignancies at a median of 6.8 years after allo‐HSCT (range, 0.12–17.3 years) for a 10‐year cumulative incidence of 3.1% (95% confidence interval [95% CI], 2–5%; all solid tumors) and 2.3% (95% CI 1–4%; excluding basal cell carcinoma and carcinoma in situ). The risk ratio of developing a second solid malignancy after allografting, compared with the general population of British Columbia adjusted for age and sex, was 1.85 (95% CI, 1.04–3.06;P= .019). In multivariate analysis, recipient age at allo‐HSCT >40 years (P= .005) and having a woman donor (P= .0008) were associated with a greater risk of developing a second solid cancer.

CONCLUSIONS.

The authors concluded that patients undergoing allografting are at increased risk of developing a second solid cancer compared with the general population, particularly those of advanced age at the time of allograft. It is noteworthy that patients who had women as graft donors had an increased risk for developing a second solid cancer. This unexpected finding is a new observation and has not been reported previously. Extended follow‐up will be needed to assess more fully the incidence and risk factors for the development of solid cancers, because the latency can be prolonged. Cancer 2007. © 2006 American Cancer Society.
Robot vision with cellular neural networks: a practical implementation of new algorithms
Authors: Pazienza Giovanni Egidio , Ponce‐García Xavier , Balsi Marco , Vilasís‐Cardona Xavier
Published: November 2006

Cellular neural networks (CNNs) are well suited for image processing due to the possibility of a parallel computation. In this paper, we present two algorithms for tracking and obstacle avoidance using CNNs. Furthermore, we show the implementation of an autonomous robot guided using only real‐time visual feedback; the image processing is performed entirely by a CNN system embedded in a digital signal processor (DSP). We successfully tested the two algorithms on this robot. Copyright © 2006 John Wiley & Sons, Ltd.
Renal care 2006: A look back
Authors: Pondrom Sue
Published: November 2006

D&T talked with several industry experts to get their take on the most important developments in the field of renal care during 2006. We explore the major changes and milestones that occurred with regard to legislation, clinical guidelines, patient care, and corporate news, and discuss the impact they may have on clinical care.
Genetic screen for mutations affecting development and function of the enteric nervous system
Authors: Kuhlman Julie , Eisen Judith S.
Published: November 2006

An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understanding of the mechanisms underlying enteric nervous system development, we screened mutagenized zebrafish for changes in the number or distribution of enteric neurons. We also established a motility assay and rescreened mutants to learn whether enteric neuron number is correlated with gastrointestinal motility in zebrafish. We describe mutations isolated in our screen that affect enteric neurons specifically, as well as mutations that affect other neural crest derivatives or have pleiotropic effects. We show a correlation between the severity of enteric neuron loss and gastrointestinal motility defects. This screen provides biological tools that serve as the basis for future mechanistic studies. Developmental Dynamics 236:118–127, 2007. © 2006 Wiley‐Liss, Inc.
Leptin: Nourishment for the immune system
Authors: Fantuzzi Giamila
Published: November 2006

Leptin, a protein produced by adipocytes, exerts several functions, including modulation of the immune response. A report in this issue of the European Journal of Immunology describes for the first time the effect of either leptin receptor deficiency or blockade on murine dendritic cell (DC) maturation, survival and function. The study describes how leptin receptor deficiency/blockade delays DC maturation and promotes apoptosis, shifts the balance between pro‐ and anti‐inflammatory cytokine production, and reduces the ability of DC to stimulate CD4+ lymphocytes. These exciting novel data add an important piece of evidence to the picture of the role of leptin in immunity and inflammation and generate the possibility that many of the effects of leptin on T lymphocytes might be mediated through DC.

See accompanying article http://dx.doi.org/10.1002/eji.200636602
On the construction of manufactured solutions for one and two‐equation eddy‐viscosity models
Authors: Eça L. , Hoekstra M. , Hay A. , Pelletier D.
Published: November 2006

This paper presents manufactured solutions (MSs) for some well‐known eddy‐viscosity turbulence models, viz. the Spalart & Allmaras one‐equation model and the TNT and BSL versions of the two‐equation k–ω model. The manufactured flow solutions apply to two‐dimensional, steady, wall‐bounded, incompressible, turbulent flows. The two velocity components and the pressure are identical for all MSs, but various alternatives are considered for specifying the eddy‐viscosity and other turbulence quantities in the turbulence models.

The results obtained for the proposed MSs with a second‐order accurate numerical method show that the MSs for turbulence quantities must be constructed carefully to avoid instabilities in the numerical solutions. This behaviour is model dependent: the performance of the Spalart & Allmaras and k–ω models is significantly affected by the type of MS. In one of the MSs tested, even the two versions of the k–ω model exhibit significant differences in the convergence properties. Copyright © 2006 John Wiley & Sons, Ltd.
A new method for direct simulations of flexible filament suspensions in non‐zero Reynolds number flows
Authors: Qi Dewei
Published: November 2006

A new method for direct simulations of flexible filament suspensions in a non‐zero Reynolds number flow is developed. For fluid domain, simulations are based on a lattice Boltzmann equation. For solid domain, a slender solid body is discretized into a chain of consecutive spherical segments contacting each other. A constraint force algorithm is proposed to warrant constant bonding distance between two neighbouring segments and non‐slip velocity conditions at the contacting points so that the flexible filament moves and rotates as a whole body. The fibre could be bent and twisted in the model. Non‐linear inertial interactions between fluid and flexible filament can be naturally studied by using this model embedded in the lattice Boltzmann scheme. The present flexible fibre method is tested by using a rigid particle method when the fibre stiffness is very large and by comparing the present results with theoretical and experimental results. It is demonstrated that the present results have a reasonable accuracy and that the computational results are consistent with the existed experimental results at non‐zero Reynolds number flows. Copyright © 2006 John Wiley & Sons, Ltd.
Corpus callosal connection mapping using cortical gray matter parcellation and DT‐MRI
Authors: Park Hae‐Jeong , Kim Jae Jin , Lee Seung‐Koo , Seok Jeong Ho , Chun Jiwon , Kim Dong Ik , Lee Jong Doo
Published: November 2006

Population maps of the corpus callosum (CC) and cortical lobe connections were generated by combining cortical gray matter parcellation with the diffusion tensor fiber tractography of individual subjects. This method is based on the fact that the cortical lobes of both hemispheres are interconnected by the corpus callosal fibers. T1‐weighted structural MRIs and diffusion tensor MRIs (DT‐MRI) of 22 right‐handed, healthy subjects were used. Forty‐seven cortical parcellations in the dorsal prefrontal cortex, ventral prefrontal cortex, sensory‐motor cortex, parietal cortex, temporal cortex, and occipital cortex were semi‐automatically derived from structural MRIs, registered to DT‐MRI, and used to identify callosal fibers. The probabilistic connections to each cortex were mapped on entire mid‐sagittal CC voxels that had anatomical homology between subjects as determined by spatial registration. According to the population maps of the callosal connections, the ventral prefrontal cortex and parts of the dorsal prefrontal cortex both project fibers through the genu and rostrum. The CC regions through which the superior frontal cortex passes extend into the posterior body. Fibers arising from the parietal lobe and occipital lobe run mainly through the splenium, while fibers arising from the sensory‐motor cortex pass through the isthmus. In general, dorsal or medial cortical lobes project fibers through the dorsal region of the CC, while lateral cortical lobes project fibers through the ventral region of the CC. The probabilistic subdivision of the CC by connecting cortical gray matter provides a more precise understanding of the CC. Hum Brain Mapp 2008. © 2006 Wiley‐Liss, Inc.
Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions
Authors: Laufs Helmut , Hamandi Khalid , Salek‐Haddadi Afraim , Kleinschmidt Andreas K. , Duncan John S. , Lemieux Louis
Published: November 2006

A cerebral network comprising precuneus, medial frontal, and temporoparietal cortices is less active both during goal‐directed behavior and states of reduced consciousness than during conscious rest. We tested the hypothesis that the interictal epileptic discharges affect activity in these brain regions in patients with temporal lobe epilepsy who have complex partial seizures. At the group level, using electroencephalography‐correlated functional magnetic resonance imaging in 19 consecutive patients with focal epilepsy, we found common decreases of resting state activity in 9 patients with temporal lobe epilepsy (TLE) but not in 10 patients with extra‐TLE. We infer that the functional consequences of TLE interictal epileptic discharges are different from those in extra‐TLE and affect ongoing brain function. Activity increases were detected in the ipsilateral hippocampus in patients with TLE, and in subthalamic, bilateral superior temporal and medial frontal brain regions in patients with extra‐TLE, possibly indicating effects of different interictal epileptic discharge propagation. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Object identification and lexical/semantic access in children: A functional magnetic resonance imaging study of word‐picture matching
Authors: Schmithorst Vincent J. , Holland Scott K. , Plante Elena
Published: November 2006

Theoretical models for lexical access to visual objects have been based mainly on adult data. To investigate the developmental aspects of object recognition and lexical access in children, a large‐scale functional MRI (fMRI) study was performed in 283 normal children ages 5–18 using a word–picture matching paradigm in which children would match an aurally presented noun to one of two pictures (line drawings). Using group Independent Component Analysis (ICA), six task‐related components were detected, including (a) the posterior superior temporal gyrus bilaterally; (b) the fusiform, inferior temporal, and middle occipital gyri bilaterally; (c) the dorsal aspect of the inferior frontal gyrus bilaterally, the left precuneus, the left superior/middle temporal gyrus, and the anterior cingulate; (d) the right medial fusiform gyrus; (e) a left‐lateralized component including the inferior/middle frontal, middle temporal, medial frontal, and angular gyri, as well as the thalamus and the posterior cingulate; and (f) the ventral/anterior aspect of the inferior frontal gyrus bilaterally. Increased activation associated with age was seen in the components (b) and (d) (ventral visual pathway) for object recognition, and (c) and (f) likely associated with semantic maintenance and response selection. Increased activation associated with task performance was seen in components (b) and (d) (ventral visual pathway) while decreased activation associated with task performance was seen in component (f) (ventral/anterior inferior frontal gyrus). The results corroborate the continued development of the ventral visual pathway throughout the developmental period. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Neural characteristics of successful and less successful speech and word learning in adults
Authors: Wong Patrick C.M. , Perrachione Tyler K. , Parrish Todd B.
Published: November 2006

A remarkable characteristic of the human nervous system is its ability to learn to integrate novel (foreign) complex sounds into words. However, the neural changes involved in how adults learn to integrate novel sounds into words and the associated individual differences are largely unknown. Unlike English, most languages of the world use pitch patterns to mark individual word meaning. We report a study assessing the neural correlates of learning to use these pitch patterns in words by English‐speaking adults who had no previous exposure to such usage. Before and after training, subjects discriminated pitch patterns of the words they learned while blood oxygenation levels were measured using fMRI. Subjects who mastered the learning program showed increased activation in the left posterior superior temporal region after training, while subjects who plateaued at lower levels showed increased activation in the right superior temporal region and right inferior frontal gyrus, which are associated with nonlinguistic pitch processing, and prefrontal and medial frontal areas, which are associated with increased working memory and attentional efforts. Furthermore, we found brain activation differences even before training between the two subject groups, including the superior temporal region. These results demonstrate an association between range of neural changes and degrees of language learning, specifically implicating the physiologic contribution of the left dorsal auditory cortex in learning success. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Elucidation of a protein signature discriminating six common types of adenocarcinoma
Authors: Bloom Gregory C. , Eschrich Steven , Zhou Jeff X. , Coppola Domenico , Yeatman Timothy J.
Published: November 2006

Pathologists are commonly facing the problem of attempting to identify the site of origin of a metastatic cancer when no primary tumor has been identified, yet few markers have been identified to date. Multitumor classifiers based on microarray based RNA expression have recently been described. Here we describe the first approximation of a tumor classifier based entirely on protein expression quantified by two‐dimensional gel electrophoresis (2DE). The 2DE was used to analyze the proteomic expression pattern of 77 similarly appearing (using histomorphology) adenocarcinomas encompassing 6 types or sites of origin: ovary, colon, kidney, breast, lung and stomach. Discriminating sets of proteins were identified and used to train an artificial neural network (ANN). A leave‐one‐out cross validation (LOOCV) method was used to test the ability of the constructed network to predict the single held out sample from each iteration with a maximum predictive accuracy of 87% and an average predictive accuracy of 82% over the range of proteins chosen for its construction. These findings demonstrate the use of proteomics to construct a highly accurate ANN‐based classifier for the detection of an individual tumor type, as well as distinguishing between 6 common tumor types in an unknown primary diagnosis setting. © 2006 Wiley‐Liss, Inc.
Monitoring a national cancer prevention program: Successful changes in cervical cancer screening in the netherlands
Authors: Rebolj Matejka , van Ballegooijen Marjolein , Berkers Louise‐Maria , Habbema Dik
Published: November 2006

The success of screening, an important cancer prevention tool, depends on the quality and efficiency of protocols and guidelines for screening and follow‐up. However, even centrally organized screening programs such as the Dutch cervical screening program occasionally show problems in performance. To improve this program, the screening scheme, follow‐up, administration and financing protocols and guidelines were thoroughly changed in 1996. This study evaluates the consequences for the performance of the national program. Five‐year coverage rate, the proportion of screened women sent to follow‐up, follow‐up compliance and duration, and the yearly number of Pap smears before and after the changes in 1996 were compared. Five‐year coverage increased substantially in the added target age groups (30–34, and 54–60 years); in the old target age group (35–53 years) it remained around 80%. The percentage of screened women sent to follow‐up decreased from almost 19–3% per screening round, due to a more restrictive use of the Pap 2 classification, and an evidence‐based cessation of follow‐up of negative smears without endocervical cells. Follow‐up compliance has improved, and the average time until a woman is either referred or rejoins the regular screening schedule, has become shorter. The total number of smears, a strong determinant of screening costs, has decreased by 20% primarily due to the changed follow‐up recommendations. In conclusion, the 1996 changes in protocols and guidelines, and their implementation have increased coverage and efficiency, and decreased the screening‐induced negative side effects. © 2006 Wiley‐Liss, Inc.
Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: Collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies
Authors:   The International Collaboration of Epidemiological Studies of Cervical Cancer
Published: November 2006

Squamous cell carcinomas account for about 80% of cancers of the uterine cervix, and the majority of the remainder are adenocarcinomas. There is limited evidence on the extent to which these histological types share a common etiology. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 8,097 women with invasive squamous cell carcinoma, 1,374 women with invasive adenocarcinoma and 26,445 women without cervical cancer (controls) from 12 epidemiological studies. Compared to controls, the relative risk of each histological type of invasive cervical cancer was increased with increasing number of sexual partners, younger age at first intercourse, increasing parity, younger age at first full‐term pregnancy and increasing duration of oral contraceptive use. Current smoking was associated with a significantly increased risk of squamous cell carcinoma (RR = 1.50, 95% CI: 1.35–1.66) but not of adenocarcinoma (RR = 0.86 (0.70–1.05)), and the difference between the two histological types was statistically significant (case‐case comparison p < 0.001). A history of screening (assessed as having had at least one previous nondiagnostic cervical smear) was associated with a reduced risk of both histological types, but the reduction was significantly greater for squamous cell carcinoma than for adenocarcinoma (RR = 0.46 (0.42–0.50) and 0.68 (0.56–0.82), respectively; case–case comparison, p = 0.002). A positive test for cervical high‐risk HPV‐DNA was a strong risk factor for each histological type, with 74% of squamous cell carcinomas and 78% of adenocarcinomas testing positive for HPV types 16 or 18. Squamous cell and adenocarcinoma of the cervix share most risk factors, with the exception of smoking. © 2006 Wiley‐Liss, Inc.
Statins and risk of cancer: A systematic review and metaanalysis
Authors: Browning Danielle R.L. , Martin Richard M.
Published: November 2006

We conducted a systematic review of the association between HMG‐CoA reductase inhibitor (statin) use and cancer risk. We searched MEDLINE, EMBASE, Web of Science, ISI Proceedings and BIOSIS Previews bibliographic databases, electronic trials registers and reference lists for potentially eligible randomized trials and observational studies. Thirty‐eight individual studies (26 randomized trials involving 103,573 participants and 12 observational studies with 826,854 participants) were included. Median follow‐up was 3.6 and 6.2 years for trials and observational studies, respectively. In metaanalyses of randomized trials, there was no evidence that statin therapy was associated with incidence of all‐cancers (26 trials; pooled risk ratio = 1.00; 95% CI 0.95–1.05; I2 = 0%) or the following site‐specific cancers: breast (7 trials; risk ratio = 1.01; 0.79–1.30; I2 = 43%), prostate (4 trials; risk ratio = 1.00; 0.85–1.17; I2 = 0%), colorectum (9 trials; risk ratio = 1.02; 0.89–1.16; I2 = 0%), lung (9 trials; risk ratio = 0.96; 0.84–1.09; I2 = 0%), genito‐urinary (5 trials; risk ratio = 0.95; 0.83–1.09; I2 = 0%), melanoma (4 trials; risk ratio = 0.86; 0.62–1.20; I2 = 17%) or gastric (1 trial; risk ratio = 1.00; 0.35–2.85). There was no evidence of differential effects by length of follow‐up, statin type (lipophilic vs. lipophobic) or potency. Trial results were generally consistent with observational studies. We conclude that statin use is not associated with short‐term cancer risk, but longer‐latency effects remain possible. © 2006 Wiley‐Liss, Inc.
Disease‐associated casein kinase I δ mutation may promote adenomatous polyps formation via a Wnt/β‐catenin independent mechanism
Authors: Tsai I‐Chun , Woolf Margaret , Neklason Deborah W. , Branford William W. , Yost H. Joseph , Burt Randall W. , Virshup David M.
Published: November 2006

The Wnt signaling pathway is critical for embryonic development and is dysregulated in multiple cancers. Two closely related isoforms of casein kinase I (CKIδ and ϵ) are positive regulators of this pathway. We speculated that mutations in the autoinhibitory domain of CKIδ/ϵ might upregulate CKIδ/ϵ activity and hence Wnt signaling and increase the risk of adenomatous polyps and colon cancer. Exons encoding the CKIϵ and CKIδ regulatory domains were sequenced from DNA obtained from individuals with adenomatous polyps and a family history of colon cancer unaffected by familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer (HNPCC). A CKIδ missense mutation, changing a highly conserved residue, Arg324, to His (R324H), was found in an individual with large and multiple polyps diagnosed at a relatively young age. Two findings indicate that this mutation is biologically active. First, ectopic ventral expression of CKIδ(R324H) in Xenopus embryos results in secondary axis formation with an additional distinctive phenotype (altered morphological movements) similar to that seen with unregulated CKIϵ. Second, CKIδ(R324H) is more potent than wildtype CKIδ in transformation of RKO colon cancer cells. Although the R324H mutation does not significantly change CKIδ kinase activity in an in vitro kinase assay or Wnt/β‐catenin signal transduction as assessed by a β‐catenin reporter assay, it alters morphogenetic movements via a β‐catenin‐independent mechanism in early Xenopus development. This novel human CKIδ mutation may alter the physiological role and enhance the transforming ability of CKIδ through a Wnt/β‐catenin independent mechanism and thereby influence colonic adenoma development. © 2006 Wiley‐Liss, Inc.
Body size, hormone therapy and risk of breast cancer in Asian–American women
Authors: Wu Anna H. , Yu Mimi C. , Tseng Chiu‐Chen , Pike Malcolm C.
Published: November 2006

Historically, breast cancer rates have been low in Asia but rates have increased substantially in Asian–Americans for reasons that are not well understood. The authors conducted a population‐based case–control study of breast cancer in Los Angeles County, which included 1,277 (450 Chinese, 352 Japanese, 475 Filipinos) women with incident, histologically confirmed breast cancer and 1,160 control subjects (486 Chinese, 311 Japanese, 363 Filipinos). A detailed in‐person interview was conducted, which included questions on menopausal hormone therapy (HT) use, height, weight in each decade of life and reproductive factors. Breast cancer risk increased with increasing recent weight in postmenopausal women (p trend = 0.015). There was a significant 16% (95% CI = 2–35%) increase in risk per 10 kg of body weight in postmenopausal women. In both premenopausal and postmenopausal women, risk increased with increasing waist to hip ratio; this remained statistically significant after adjustment for recent weight in all subjects combined (p trend = 0.042). The increased risk associated with high recent weight in postmenopausal women was more apparent for women with high waist to hip ratio (p trend = 0.013). Use of HT was a significant risk factor; risk increased 26% per 5 years of current use of estrogen and progestin therapy (p trend = 0.017). The increased risk associated with high body weight was observed irrespective of HT use. Use of HT and high body size might have contributed to the rapid increase of breast cancer in Asian–Americans. © 2006 Wiley‐Liss, Inc.
Identification of HLA‐A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung
Authors: Sugaya Masakazu , Takenoyama Mitsuhiro , Shigematsu Yoshiki , Baba Tetsuro , Fukuyama Takashi , Nagata Yoshika , Mizukami Makiko , So Tetsuya , Ichiki Yoshinobu , Yasuda Manabu , So Tomoko , Hanagiri Takeshi , Sugio Kenji , Yasumoto Kosei
Published: November 2006

The aim of the present study was to elucidate the tumor‐specific cellular immunological responses occurring in a patient with large cell carcinoma of the lung who had no evidence of recurrence following surgical resections of both a primary lung lesion and a metastatic adrenal lesion. We analyzed an autologous tumor‐specific cytotoxic T lymphocytes (CTL clone F2b), which were HLA‐A*2402 restricted from regional lymph node lymphocytes. The F2b possessed T cell receptor (TCR) using the Vα5 and Vβ7 gene segment. The existence of precursor CTL (pCTL) against autologous tumor cells (A904L) was analyzed using CTL clone‐specific PCR. Lymphocytes with the same TCR as F2b were detected in the primary tumor tissue, regional lymph node and the peripheral blood collected from the patient 3 years after the operation. Using the F2b, we identified a cDNA clone encoding the tumor antigen using cDNA expression cloning method. The gene was found to encode splicing variant of the Tara gene. Finally, we identified the 9‐mer Ag peptide, using constructions of mini‐genes. The F2b recognized 3 out of 7 HLA‐A24 positive allogeneic tumor cell lines and in 1 out of 7 HLA‐A24 negative allogeneic tumor cell lines when transfected with HLA‐A24. This peptide is therefore considered to be potentially useful for performing specific immunotherapy in a significant proportion of lung cancer patients bearing HLA‐A24. © 2006 Wiley‐Liss, Inc.
Pyrazolo–pyrimidine‐derived c‐Src inhibitor reduces angiogenesis and survival of squamous carcinoma cells by suppressing vascular endothelial growth factor production and signaling
Authors: Donnini Sandra , Monti Martina , Castagnini Cinzia , Solito Raffaella , Botta Maurizio , Schenone Silvia , Giachetti Antonio , Ziche Marina
Published: November 2006

Src tyrosine kinase family cooperates with activated growth factor receptors to regulate growth, invasion and metastasis. The authors examined the influence of a novel c‐Src inhibitor, 1l, derived from 4‐amino‐substituted‐pyrazolo–pyrimidines, on tumor angiogenesis and on the angiogenic output of squamous carcinoma cells, A431 and SCC‐4. The effect of 1l was assessed on growth and microvessel density in A431 tumors and its effect compared with the established c‐Src inhibitor PP‐1. The effects of c‐Src inhibition were investigated on vascular endothelial growth factor (VEGF) expression and activity in tumor cells grown in vivo and in vitro, as well as on VEGF mediated signaling and on endothelial cell functions. Nanomolar concentrations of 1l decreased tumor volume promoted by A431 implanted in nude mice, without affecting in vitro cell tumor survival. This effect was related to 1l inhibition of VEGF production, and secondary to an effect on tumor microvessel density. The rabbit cornea assay confirmed that 1l markedly decreased neovessel growth induced by VEGF. In cultured endothelial cells, 1l inhibited the VEGF‐induced phosphorylation on tyr416 of c‐Src, resulting in a reduced cell proliferation and invasion. Consistently, 1l dowregulated endothelial nitric oxide synthase, MAPK‐extracellular receptor kinase 1–2 (ERK1‐2) activity and matrix metalloproteinases (MMP‐2/MMP‐9), while the tissue inhibitors of metalloproteinases (TIMP2/TIMP‐1) were upregulated. These results demonstrate that nM concentrations of c‐Src kinase inhibitors (1l and PP‐1), by reducing the production of VEGF released by tumor cell and its endothelial cell responses, have a highly selective antiangiogenesis effect, which might be useful in combination therapies. © 2006 Wiley‐Liss, Inc.
Dietary polyphenolic phytochemicals—promising cancer chemopreventive agents in humans? A review of their clinical properties
Authors: Thomasset Sarah C. , Berry David P. , Garcea Giuseppe , Marczylo Timothy , Steward William P. , Gescher Andreas J.
Published: November 2006

Epidemiological and preclinical evidence suggests that polyphenolic phytochemicals exemplified by epigallocatechin gallate from tea, curcumin from curry and soya isoflavones possess cancer chemopreventive properties. Whilst such naturally occurring polyphenols have been the subject of numerous mechanistic studies in cells, information on their clinical properties, which might help assess their promise as human cancer chemopreventive agents, is scarce. Therefore, we present a review of pilot studies and trials with a cancer chemoprevention‐related rationale, in which either healthy individuals or patients with premalignant conditions or cancer received polyphenolic phytochemicals. The review identifies trial design elements specifically applicable to polyphenolic phytochemicals. The available evidence for tea polyphenols tentatively supports their advancement into phase III clinical intervention trials aimed at the prevention of progression of prostate intraepithelial neoplasia, leukoplakia or premalignant cervical disease. In the case of curcumin and soya isoflavones more studies in premalignacies seem appropriate to optimise the nature and design of suitable phase III trials. The abundance of flavonoids and related polyphenols in the plant kingdom makes it possible that several hitherto uncharacterised agents with chemopreventive efficacy are still to be identified, which may constitute attractive alternatives to currently used chemopreventive drugs. © 2006 Wiley‐Liss, Inc.
Loss of chromosomal integrity drives rat mammary tumorigenesis
Authors: Goepfert Thea M. , Moreno‐Smith Myrthala , Edwards David G. , Pathak Sen , Medina Daniel , Brinkley W.R.
Published: November 2006

Breast cancer incidence varies with diet and other environmental influences, including carcinogen exposure. However, the effects of carcinogens on cell growth control pathways are poorly understood. Here, we have examined processes that are activated in the mammary glands of rats treated with 1‐methyl‐1‐nitrosourea (MNU). This synthetic carcinogen was used to study events occurring during mammary tumor initiation and development. In female Wistar‐Furth rats, given 1 dose of MNU beginning at 50 days of age, 84% of the rats developed tumors by 46 weeks of age (latency 13–15 weeks). Changes in the gland occurred as early as 1‐day post‐MNU. Cells exhibited DNA damage, leading to chromosomal instability, supernumerary centrosomes and higher levels of Aurora A; these events correlated with the appearance of preneoplasia in the glands. In mammary tumors, elevated numbers of centrosomes coincided with genomic instability. Tumors were transplanted into syngeneic hosts and subsequent tumor generations displayed the same marker chromosomes in mostly aneuploid metaphases with hyperdiploid numbers of chromosomes, suggesting that clonality and aneuploidy were passed on from one generation to the next. Collectively, these data suggest that the carcinogen MNU induces changes resulting in genetic instability detectable before hyperplasia and tumors develop in the rat mammary gland. © 2006 Wiley‐Liss, Inc.
Carbohydrate intake, glycemic index and glycemic load in relation to risk of endometrial cancer: A prospective study of Swedish women
Authors: Larsson Susanna C. , Friberg Emilie , Wolk Alicja
Published: November 2006

The associations of carbohydrate intake, glycemic index and glycemic load with endometrial cancer risk were examined among 61,226 participants of the Swedish Mammography Cohort who were cancer‐free at enrollment between 1987 and 1990 and completed a food frequency questionnaire. During a mean follow‐up of 15.6 years, through June 2005, 608 incident cases of endometrial adenocarcinoma were diagnosed. We observed no overall association between carbohydrate intake, glycemic index or glycemic load and incidence of endometrial cancer; the rate ratios (RRs) for the highest versus the lowest quintile were 1.12 (95% CI, 0.85–1.47) for carbohydrate intake, 1.00 (95% CI, 0.77–1.30) for glycemic index and 1.15 (95% CI, 0.88–1.51) for glycemic load. However, among obese women (body mass index, BMI ≥30 kg/m2), endometrial cancer incidence was nonsignificantly elevated in the top versus bottom quintiles of carbohydrate intake (RR, 1.68; 95% CI, 0.86–3.29) and glycemic load (RR, 1.57; 95% CI, 0.82–2.99). In a subanalysis of women who completed a follow‐up questionnaire in 1997, which collected information on physical activity, carbohydrate intake and glycemic load were positively related to endometrial cancer risk among overweight women (BMI ≥25 kg/m2) with low physical activity. In this subgroup, the multivariate RRs comparing extreme quartiles were 1.90 (95% CI, 0.84–4.31) for carbohydrate intake and 2.99 (95% CI, 1.17–7.67) for glycemic load. Results from this cohort study suggest that a high carbohydrate intake and a high glycemic load may increase the risk of endometrial cancer among overweight women with low physical activity. © 2006 Wiley‐Liss, Inc.
SV40 and human cancer: A review of recent data
Authors: Shah Keerti V.
Published: November 2006

An unknown proportion of formalin‐inactivated poliovirus vaccine lots administered to millions of US residents between 1955 and 1963 was contaminated with small amounts of infectious simian virus 40 (SV40), a polyomavirus of the rhesus macaque. It has been reported that mesothelioma, brain tumors, osteosarcoma and non‐Hodgkin lymphoma (NHL) contain SV40 DNA sequences and that SV40 infection introduced into humans by the vaccine probably contributed to the development of these cancers. The Immunization Safety Review Committee of the Institute of Medicine (IOM) reviewed this topic in 2002. The present review of recent studies showed that the earlier results describing the recovery of SV40 DNA sequences from a large proportion of the above tumors were not reproducible and that most studies were negative. Contamination with laboratory plasmids was identified as a possible source of false positive results in some previous studies. The low‐level immunoreactivity of human sera to SV40 was very likely the result of cross‐reactivity with antibodies to the SV40‐related human polyomaviruses BKV and JCV, rather than of authentic SV40 infection. SV40 sero‐reactivity in patients with the suspect tumors was no greater than that in controls. In epidemiologic studies, the increased incidence of some of the suspect tumors in the 1970s to 1980s was not related to the risk of exposure to SV40‐contaminated vaccines. In summary, the most recent evidence does not support the notion that SV40 contributed to the development of human cancers. © 2006 Wiley‐Liss, Inc.