bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Xanthine Oxidase by Thiosemicarbazones, Hydrazones and Dithiocarbazates Derived from Hydroxy‐Substituted Benzaldehydes
Authors: Leigh Maria , Raines Daniel J. , Castillo Carmen E. , Duhme‐Klair Anne K.
Published: April 2011

Nonpurine xanthine oxidoreductase (XOR) inhibitors represent important alternatives to the purine analogue allopurinol, which is still the most widely used drug in the treatment of conditions associated with elevated uric acid levels in the blood. By condensing mono‐, di‐ and trihydroxybenzaldehydes with aromatic thiosemicarbazides, aryl hydrazides and dithiocarbazates, three series of structurally related Schiff bases were synthesised, characterised and tested for XOR inhibitory activity. Hydroxy substitution in the para‐position of the benzaldehyde component was found to confer high inhibitory activities. Acyl hydrazones were generally less potent than thiocarbonyl‐containing Schiff bases. Within the thiosemicarbazone series, chloro and cyano substituents in the para‐position of the thiosemicarbazide unit increased activities further, up to potencies approximately four‐times higher than that of the benchmark allopurinol, as measured under the same assay conditions. In order to illustrate the potential of the Schiff bases to bind directly to the molybdenum centre in the active site of the enzyme, a representative example (H2L) of each inhibitor series was co‐ordinated to a cis‐dioxomolybdenum(VI) unit, and the resulting complexes, [MoO2(L)MeOH], were structurally characterised. Subsequent steady‐state kinetic investigations, however, indicated mixed‐type inhibition, similar to that observed for inhibitors known to bind within the substrate access channel of the enzyme, remote from the Mo centre. Enzyme co‐crystallisation studies are thus required to determine the exact binding mode. Finally, the coordination of representative inhibitors to copper(II) gave rise to significantly decreased IC50 values, revealing an additive effect that merits further investigation.
Detection of second malignancies during long‐term follow‐up of testicular cancer survivors
Authors: Buchler Tomas , Kubankova Petra , Boublikova Ludmila , Donatova Zuzana , Foldyna Martin , Kanakova Jana , Kordikova Drahomira , Kupec Martin , Nepomucka Jana , Vorsilkova Eva , Abrahamova Jitka
Published: April 2011

BACKGROUND:

Second cancers are an important cause of mortality and morbidity in long‐term survivors of testicular germ cell tumors (TGCTs). Studies on the impact of follow‐up for the first tumor on the outcome of second malignancies are lacking. The aim of this study was to study the details of diagnosis of second cancers and the role of focused oncology follow‐up.

METHODS:

Medical records and the electronic database of a tertiary referral center for germ cell neoplasms were searched for second cancers diagnosed in TGCT survivors. In a database of 1057 patients, 63 cases of metachronous second malignancies (26 contralateral testicular cancers and 37 nontesticular cancers) were found in 57 patients. Long‐term oncology follow‐up consisted of yearly history, physical examination, germ cell tumor markers, and imaging including abdominal computed tomography (CT) scans and chest x‐ray.

RESULTS:

The second malignancies occurred after a medium follow‐up of 9.9 years (range, 1.1‐33 years) after the diagnosis of the first tumor. Only 17 (27%) of the 63 second tumors were detected by oncology follow‐up investigations, and a further 12 (29%) were detected by nononcology physicians during a preplanned clinical visit. In 34 (54%) cases, patients themselves or their relatives initiated a clinical appointment because of symptoms. Follow‐up investigations all had low yields for the detection of second malignancies, although CT imaging did detect several cases of cancer at an early stage.

CONCLUSIONS:

In this retrospective study, most second cancers occurring in long‐term TGCT survivors were missed by regular oncology follow‐up that included yearly physical examination, tumor marker, and imaging. Cancer 2011;. © 2011 American Cancer Society.
Comorbidity and competing risks for mortality in men with prostate cancer
Authors: Daskivich Timothy J. , Chamie Karim , Kwan Lorna , Labo Jessica , Dash Atreya , Greenfield Sheldon , Litwin Mark S.
Published: April 2011

BACKGROUND:

Accurate estimation of life expectancy is essential for men deciding between aggressive and conservative treatment of prostate cancer. The authors sought to assess the competing risks of nonprostate cancer and prostate cancer mortality among men with differing Charlson comorbidity index scores and tumor risks.

METHODS:

The authors conducted a retrospective study of 1482 men with nonmetastatic prostate cancer diagnosed from 1997 to 2004 at the Greater Los Angeles and Long Beach Veterans Affairs Medical Centers. They performed Kaplan‐Meier and competing risks regression analyses to assess survival outcomes.

RESULTS:

After a mean follow‐up of 6.0 years, 370 (25%) men died from other causes, whereas 44 (3%) died of prostate cancer. At 10 years after diagnosis, men with Charlson scores 0, 1, 2, and 3+ had nonprostate cancer mortality rates of 17%, 34%, 52%, and 74%, respectively. In competing risks regression analysis, each point increase in Charlson score was associated with a 2‐fold increase in hazard of nonprostate mortality. Men with Charlson 3+ had 8.5× the hazard of death from other causes, compared with men with the lowest scores (subhazard ratio, 8.5; 95% confidence interval, 6.2‐11.7). After stratification by tumor risk, nonprostate mortality rates remained markedly elevated among men with higher Charlson scores, whereas prostate cancer mortality was rare, especially among low‐risk and intermediate‐risk groups (0.4%, 3%, and 8% for low, intermediate, and high risk, respectively).

CONCLUSIONS:

Men with the highest Charlson scores should consider conservative management of low‐risk and intermediate‐risk tumors, given their exceedingly high risk of death from other causes and low risk of prostate cancer mortality. Cancer 2011;. © 2011 American Cancer Society.
Evaluating the serial use of the myelofibrosis symptom assessment form for measuring symptomatic improvement
Authors: Mesa Ruben A. , Kantarjian Hagop , Tefferi Ayalew , Dueck Amylou , Levy Richard , Vaddi Kris , Erickson‐Viitanen Susan , Thomas Deborah A. , Cortes Jorge , Borthakur Gautam , Pardanani Animesh D. , Estrov Zeev , Verstovsek Srdan
Published: April 2011

BACKGROUND:

Symptomatic burden from constitutional symptoms, anemia, and splenomegaly‐related symptoms are common and morbidity inducing in patients with myelofibrosis (MF). The authors previously developed a MF‐specific instrument for capturing the burden of MF‐associated disease‐related symptoms, the Myelofibrosis Symptom Assessment Form.

METHODS:

The authors evaluated the usefulness of serial administration of the Myelofibrosis Symptom Assessment Form as an instrument for the assessment of symptomatic burden and improvement in conjunction with the therapeutic clinical trial of the open label phase 2 trial of the JAK1 and JAK2 inhibitor INCB018424 in patients with MF.

RESULTS:

The analysis cohort of 87 patients treated in this trial demonstrated that the instrument was comprehensive and sensitive to symptoms present at trial enrollment. In addition, baseline Myelofibrosis Symptom Assessment Form symptom scores correlated well with objective parameters such as splenomegaly and impaired performance status assessed by the 6‐minute walk test. Serial administration while on therapy with INCB018424 demonstrated the instrument to be sensitive to symptomatic change, and that improvements in symptoms correlated well with objective improvements in both weight loss and performance status (6‐minute walk test).

CONCLUSIONS:

The use of the Myelofibrosis Symptom Assessment Form in this phase 2 trial helped characterize the symptomatic improvements observed with use of INCB018424 in MF patients. In an era of many targeted therapies undergoing testing for MF with potential symptomatic benefit, the Myelofibrosis Symptom Assessment Form may provide a useful tool for objective symptomatic assessment and potentially allow some nonrandomized comparison between therapeutic agents. Cancer 2011;. © 2011 American Cancer Society.
The effect of streamflow reductions on aquatic habitat availability and fish and macroinvertebrate assemblages in coastal plain streams
Authors: Procopio Nicholas A.
Published: April 2011

The purpose of this study was to estimate changes to aquatic habitat availability and fish and aquatic macroinvertebrate assemblages in coastal plain streams that may result from groundwater withdrawals. Hypothetical streamflow reductions of 5, 10, 20, and 30% of average annual streamflow and the 7‐day low flow were calculated for 14 study sites. Using study‐site streamflow and channel morphology data, relationships were developed to estimate five physical habitat metrics including average stream width, stream depth, stream cross‐sectional area, stream‐reach volume, and stream velocity. A second set of relationships was then developed to estimate the percentage reduction to each habitat metric under the hypothetical streamflow reduction scenarios. The average percentage decrease and variability of each habitat metric increased with successive streamflow reductions. Average percentage decreases in stream width, stream depth, stream cross‐sectional area, and stream‐reach volume were more pronounced for the reductions of average flow, whereas the average percentage decreases in stream velocity were more pronounced for the reductions of low flow. Models derived from a separate fish and macroinvertebrate study were used to estimate assemblage structure responses based on hypothetical reductions in average annual streamflow. The results of this study can be used to estimate the potential impact of groundwater withdrawals and subsequent streamflow reductions on available aquatic habitat and changes to fish and macroinvertebrate assemblages in coastal plain streams. Copyright © 2011 John Wiley & Sons, Ltd.
Modulation of human T‐cell functions by reactive nitrogen species
Authors: Kasic Tihana , Colombo Piergiuseppe , Soldani Cristiana , Wang Chiuhui M. , Miranda Elena , Roncalli Massimo , Bronte Vincenzo , Viola Antonella
Published: April 2011

Previous studies have suggested that T‐lymphocyte dysfunction might be attributable to nitrative stress induced by reactive nitrogen species (RNS). In this manuscript, we explored this hypothesis and provided a direct demonstration of the inhibitory effects of RNS on human T‐cell signaling, activation, and migration. We found that short exposure of human T cells to RNS induced tyrosine phosphorylation of several proteins, including the CD3ζ chain of the TCR complex, and release of Ca2+ from intracellular stores. When the exposure to RNS was prolonged, T cells became refractory to stimulation, downregulated membrane receptors such as CD4, CD8, and chemokine receptors, and lost their ability to migrate in response to chemokines. Since substantial protein nitration, a hallmark of nitrative stress, was observed in various human cancers, intratumoral generation of RNS might represent a relevant mechanism for tumor evasion from immune surveillance.
Stabilin‐1/CLEVER‐1, a type 2 macrophage marker, is an adhesion and scavenging molecule on human placental macrophages
Authors: Palani Senthil , Maksimow Mikael , Miiluniemi Mari , Auvinen Kaisa , Jalkanen Sirpa , Salmi Marko
Published: April 2011

Stabilin‐1/common lymphatic endothelial and vascular endothelial receptor‐1 (CLEVER‐1) is a multidomain protein present in lymphatic and vascular endothelial cells and type 2 immunosuppressive macrophages. In adults, stabilin‐1/CLEVER‐1 is a scavenging receptor and an adhesion molecule, but much less is known about its role during development. Here, we studied the expression and functions of macrophage stabilin‐1/CLEVER‐1 in human placenta and during human ontogeny. Using newly generated mAbs, we found that stabilin‐1/CLEVER‐1 is expressed on virtually all macrophages in term placenta, both in the decidua and in the placental villi. Placental stabilin‐1/CLEVER‐1 was involved in the scavenging of Ac‐LDL (acetylated low density lipoprotein) and in the uptake of fluorescently labeled model antigen OVA. siRNA‐mediated suppression of stabilin‐1/CLEVER‐1 altered the cytokine profile produced by placental macrophages. Stabilin‐1/CLEVER‐1 on placental macrophages mediated their adhesion to placental vessels and supported their transmigration through vascular endothelium. Finally, we found that stabilin‐1/CLEVER‐1 is induced very early in fetal macrophages, high endothelial venules, and lymphatic vessels in multiple lymphatic organs. Together, these data suggest that macrophage stabilin‐1/CLEVER‐1 can potentially regulate leukocyte migration and scavenging during the development of the placenta and fetus.
Two‐Phase Approach to High‐Quality, Oil‐Soluble, Near‐Infrared‐Emitting PbS Quantum Dots by Using Various Water‐Soluble Anion Precursors
Authors: Deng Dawei , Cao Jie , Xia Junfei , Qian Zhiyu , Gu Yueqing , Gu Zhongze , Akers Walter John
Published: April 2011

Colloidal PbS quantum dots (QDs) with tunable photoemission throughout the near‐infrared (NIR) region (ca. 750–1000 nm) were synthesized by a two‐phase approach. Here, oil‐soluble lead oleate formed by a reaction of lead acetate and oleic acid (OA, the capping agent) in n‐decane at 130 °C was used as lead precursor, and water‐soluble Na2S, thioacetamide (TAA), and thiourea, each having a different reactivity, were used as sulfur sources. When an n‐decane solution of lead precursor and an aqueous solution of sulfur precursor were mixed at the appointed temperature, oil‐soluble, near‐infrared‐emitting PbS QDs were achieved. In this study, we investigated the influence of the reactivity of water‐soluble sulfur sources on the synthesis of PbS QDs. The morphology and crystal structure of the as‐prepared PbS QDs were characterized by (high‐resolution) transmission electron microscopy (TEM), selected area electron diffraction (SAED), and X‐ray diffraction (XRD).
Solvent extraction of highly valuable oxygenated terpenes from lemon essential oil using a polypropylene membrane contactor: potential and limitations
Authors: Dupuy A. , Athes V. , Schenk J. , Jenelten U. , Souchon I.
Published: April 2011

In this study, the technology of membrane contactors was assessed for the liquid–liquid extraction of highly valuable oxygenated terpenes from lemon essential oil using mixtures of water and ethanol as solvents (20–66% v/v ethanol). The main expected benefit of using membrane contactors in this application was the elimination of the phase separation step, which can be difficult in these types of systems, which are characterized by a low interfacial tension and the presence of natural surfactants. A commercially available polypropylene hollow fibre contactor (Liqui‐Cel® 2.5 × 8 with X30 fibres) was used in this study. Stabilizing the interface between the hydro‐alcoholic solvent and lemon essential oil in membrane pores proved difficult (breakthrough pressure below 0.2 bar), even with solvents containing only 20% v/v ethanol. This problem was probably due to defects in the membrane material such as the presence of large pores (up to 4 µm in diameter). Nonetheless, the hydro‐alcoholic extract remained emulsion free throughout extraction, considered to be an improvement since it eliminated the time‐consuming decantation step (process intensification). High mass transfer coefficients up to 1.08 × 10−6 m/s were obtained for the tracer of oxygenated terpenes and a solvent with 66% v/v ethanol. The membrane never represented more than 25% of the total resistance to mass transfer. We demonstrated the high potential of using membrane contactors for this application, provided that improvements were performed on membrane materials. Copyright © 2011 John Wiley & Sons, Ltd.
Study on umami taste: the MSG taste‐enhancing activity of N2‐alkyl and N2‐alkanoyl‐5′‐guanylic acids having a sulfoxide group inside the N2‐substituent
Authors: Morelli Carlo F. , Manitto Paolo , Speranza Giovanna
Published: April 2011

N2‐alkyl and N2‐alkanoyl derivatives of guanosine 5′‐phosphate bearing a sulfoxide group into the side chain (3b,e; 4b) were synthesized and tested for their synergistic effect with monosodium‐l‐glutamate (MSG), which is the prototypical substance imparting umami taste to savoury‐based foods. Capacities to enhance the taste intensity of MSG were estimated (as γ values) through subjective comparisons of MSG/5′‐nucleotide mixtures in water with appropriate solutions of MSG alone, followed by statistical treatment (Probit method) of the resulting responses. The synergistic activity of each sulfoxide toward MSG resulted to be lower than that of the corresponding sulfide. Copyright © 2011 John Wiley & Sons, Ltd.
CD13: Waving the flag for a novel cancer stem cell target
Authors: Christ Bruno , Stock Peggy , Dollinger Matthias M.
Published: April 2011

Cancer stem cells (CSCs) are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. They are thought to be involved in tumor resistance to chemo/radiation therapy and tumor relapse and progression. However, neither their existence nor their identity within many cancers has been well defined. Here, we have demonstrated that CD13 is a marker for semiquiescent CSCs in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. CD13+ cells predominated in the G0 phase of the cell cycle and typically formed cellular clusters in cancer foci. Following treatment, these cells survived and were enriched along the fibrous capsule where liver cancers usually relapse. Mechanistically, CD13 reduced ROS-induced DNA damage after genotoxic chemo/radiation stress and protected cells from apoptosis. In mouse xenograft models, combination of a CD13 inhibitor and the genotoxic chemotherapeutic fluorouracil (5-FU) drastically reduced tumor volume compared with either agent alone. 5-FU inhibited CD90+ proliferating CSCs, some of which produce CD13+ semiquiescent CSCs, while CD13 inhibition suppressed the self-renewing and tumor-initiating ability of dormant CSCs. Therefore, combining a CD13 inhibitor with a ROS-inducing chemo/radiation therapy may improve the treatment of liver cancer.
Can oil diversify away the unpriced risk of a portfolio?
Authors: Cifarelli Giulio , Paladino Giovanna
Published: April 2011

The growing presence of financial operators in the oil market has brought about the diffusion of techniques—such as feedback trading—which lead to departures of prices from their fundamental values and increase their variability. Oil price changes are here associated with changes in stocks, bonds and effective USD exchange rate. The feedback trading mechanism is combined with an ICAPM scheme. This original model is estimated in a four asset CCC GARCH non‐linear framework, where the risk premium and the feedback trading components of the conditional means are multiplicative functions of the system's conditional variances and covariances. The empirical analysis, which encompasses the 2008–2009 financial crisis, identifies a structural change in the year 2000. From then on oil returns tend to become more reactive to the remaining assets of the model and feedback trading more pervasive. A comparison is drawn between three and four asset minimum variance portfolios in the two subperiods, 1992–1999 and 2000–2009. Indeed, the trade‐off between risk and returns—measured here by the average return per unit of risk index—indicates that in the last decade, oil diversifies away the empirical risk of our portfolio. Copyright © 2011 John Wiley & Sons, Ltd.
Incorporating spiritual beliefs into a cognitive model of worry
Authors: Rosmarin David H. , Pirutinsky Steven , Auerbach Randy P. , Björgvinsson Thröstur , Bigda‐Peyton Joseph , Andersson Gerhard , Pargament Kenneth I. , Krumrei Elizabeth J.
Published: April 2011

Cognitive theory and research have traditionally highlighted the relevance of the core beliefs about oneself, the world, and the future to human emotions. For some individuals, however, core beliefs may also explicitly involve spiritual themes. In this article, we propose a cognitive model of worry, in which positive/negative beliefs about the Divine affect symptoms through the mechanism of intolerance of uncertainty. Using mediation analyses, we found support for our model across two studies, in particular, with regards to negative spiritual beliefs. These findings highlight the importance of assessing for spiritual alongside secular convictions when creating cognitive‐behavioral case formulations in the treatment of religious individuals. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–10, 2011.
Training competent psychologists in the field of child maltreatment
Authors: Damashek Amy , Balachova Tatiana , Bonner Barbara
Published: April 2011

Child maltreatment is a serious threat to children's physical and psychological well‐being; therefore, it is critically important to develop high‐quality educational programs to train psychologists in effectively addressing child abuse and neglect. Various health care disciplines and areas within the field of psychology have established competencies as a guide for student training curricula; however, none have been established for the area of child maltreatment. The present article presents training competencies for the field of child maltreatment that have been developed from a program designed to train psychology graduate students to practice and conduct research in child maltreatment. The competencies have been divided into eight core areas including assessment, treatment, multidisciplinary collaboration, advocacy, ethics, research, research ethics, and professional development. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–6, 2011.
The modified wells score accurately excludes pulmonary embolus in hospitalized patients receiving heparin prophylaxis
Authors: Bahia Amit , Albert Richard K.
Published: April 2011

BACKGROUND:

The usefulness of the Wells score has not been assessed in hospitalized patients receiving prophylactic heparin.

METHODS:

Retrospective, observational study of hospitalized patients receiving prophylactic heparin who underwent contrast‐enhanced chest computed tomography (CT) for a concern of pulmonary embolism (PE) more than 2 days after admission. Patients with contraindications to, or interruptions in, prophylactic heparin were excluded. The modified (eg, dichotomous) Wells score was retrospectively calculated by reviewing each patient's record. Requesting a d‐dimer was taken to mean that alternate diagnoses were of equal or greater likelihood than acute PE.

RESULTS:

From January 2006 through December 2007, 286 patients met inclusion criteria. Pulmonary embolus diagnosed by CT was present in 20 patients (7%). The sensitivity, specificity, positive and negative predictive values of a Wells score ≥4.0 were 95%, 27%, 9% and 99%, respectively. A d‐dimer was ordered in 70 of the 74 PE‐unlikely cases, was elevated in 67, and falsely positive in all but 1.

CONCLUSIONS:

The prevalence of PE in hospitalized patients receiving prophylactic heparin is lower than in cohorts from which the Wells prediction criteria were derived and validated. A modified Wells score <4 safely excludes PE in such patients and reduces the need for CT. D‐dimer testing adds nothing to the evaluation. Journal of Hospital Medicine 2011;. © 2011 Society of Hospital Medicine.
An alternative to R2 for assessing linear models of effect size
Authors: Aloe Ariel M. , Becker Betsy Jane , Pigott Therese D.
Published: April 2011

Reviewers often use regression models in meta‐analysis (‘meta‐regressions’) to examine the relationships between effect sizes and study characteristics. In this paper, we propose and illustrate the use of an index (R) that expresses the amount of variance in the outcome that is explained by the meta‐regression model. The values of R2 obtained from the standard computer output for linear models of effect size in the meta‐analysis context are typically too small, because the typical R2 considers sampling variance to be unexplained whereas in meta‐analysis it can be quantified. Although the idea of removing the unexplainable variance from the estimator of variance accounted for in meta‐analysis is not new (Cook et al., 1992; Raudenbush, 1994) we explicitly define four estimators of variance explained, and illustrate via two examples that the typical R2 obtained in a linear model of effect size is always lower than our indices. Thus, the typical R2 underestimates the explanatory power of linear models of effect sizes. Our four estimators improve upon typical weighted R2 values. Copyright © 2011 John Wiley & Sons, Ltd.
Use of quality control charts for detection of outliers and temporal trends in cumulative meta‐analysis
Authors: Kulinskaya Elena , Koricheva Julia
Published: April 2011

Cumulative meta‐analysis (CMA) aims to aggregate accumulating evidence. Essentially a visual tool, CMA should be supplemented by formal statistical methods for assessment of the significance of the accumulating evidence, and for detection of temporal trends in effect sizes. These methods should also take into account multiple testing inherent in CMA. We review the existing methods for detection of temporal trends in effect sizes and suggest a new approach, namely the use of standard quality control (QC) charts, in particular X charts and CUSUM charts, to detect possible outliers and trends over time. We discuss the application of the QC charts to four popular measures of effect size: the odds ratios, the relative risks, the correlation coefficients and the standardized mean differences. Applications of QC charts are illustrated by three meta‐analysis examples from medicine, ecology and evolutionary biology. Copyright © 2011 John Wiley & Sons, Ltd.
Cancer therapy based on oncogene addiction
Authors: McCormick Frank
Published: April 2011

Tumor cells contain multiple mutations, yet they often depend on continued expressed of a single oncoprotein for survival. Targeting these proteins has led to dramatic responses. Unfortunately, patients usually progress, through drug resistance or adaptive resistance through reprogramming of signaling networks. The Ras‐MAPK pathway provides examples of these successes and failures, and has revealed unexpected degrees of oncogene addiction and signaling complexity that are likely to be useful lessons for the future of targeted therapy. J. Surg. Oncol. 2011;103:464–467. © 2011 Wiley‐Liss, Inc.
Detection and prognostic impact of micrometastasis in colorectal cancer
Authors: Sirop Saad , Kanaan Mohammed , Korant Alpesh , Wiese David , Eilender David , Nagpal Sunil , Arora Madan , Singh Trevor , Saha Sukamal
Published: April 2011

Review of literature was performed on studies with prognostic impact of micrometastasis in colorectal cancer. Among 16 studies included, micrometastasis was detected in 26.5% of patients. Most analysis revealed that micrometastasis carries a poorer prognosis compared to node negative disease (NND). The results of those studies were compared with our pilot study of 109 patients with colon cancer, showing improved prognosis of micrometastasis after being upstaged and treated with chemotherapy when compared with NND. J. Surg. Oncol. 2011;103:534–537. © 2011 Wiley‐Liss, Inc.
Experimental models to study lymphatic and blood vascular metastasis
Authors: Chen Lu , Hann Byron , Wu Lily
Published: April 2011

As a model system for the understanding of human cancer, the mouse has proved immensely valuable. Indeed, studies of mouse models have helped to define the nature of cancer as a genetic disease and demonstrated the causal role of genetic events found in tumors. As an experimental platform, they have provided critical insight into the process of tumor metastasis in the lymphovascular system. Once viewed with skepticism, mouse models are now an integral arm of basic and clinical cancer research. The use of a genetically tractable organism that shares organ systems and an immense degree of genetic similarity to humans provides a means to examine multiple features of human disease. Mouse models enable development and testing of new approaches to disease prevention and treatment, identification of early diagnostic markers and novel therapeutic targets, and an understanding of the in vivo biology and genetics of tumor initiation, promotion, progression, and metastasis. This review summarizes recent mouse models for lymphangiogenesis and the process of lymphovascular metastasis, focusing on the use of the cornea as an experimental platform for lymphangiogenesis in inflammation and immunity, and on the use of molecular and viral vector mediated imaging and to identify and monitor lymph node metastases of prostate cancer. J. Surg. Oncol. 2011;103:475–483. © 2011 Wiley‐Liss, Inc.
Diagnostic and therapeutic imaging for cancer: Therapeutic considerations and future directions
Authors: Roach Mack , Alberini Jean‐Louis , Pecking Alain Paul , Testori Alessandro , Verrecchia Francesco , Soteldo Javier , Ganswindt Ute , Joyal John L. , Babich John W. , Witte Russell S. , Unger Evan , Gottlieb Ronald
Published: April 2011

As cancer treatment cost soar and the mantra for “personalized medicine” grows louder, we will increasingly be searching for solutions to these diametrically opposed forces. In this review we highlight several exciting novel imaging strategies including MRI, CT, PET SPECT, sentinel node, and ultrasound imaging that hold great promise for improving outcomes through detection of lymph node involvement. We provide clinical data that demonstrate how these evolving strategies have the potential to transform treatment paradigms. J. Surg. Oncol. 2011;103:587–601. © 2011 Wiley‐Liss, Inc.
Prostate cancer stem cells and their potential roles in metastasis
Authors: Li Hangwen , Tang Dean G.
Published: April 2011

Most solid tumors have now been reported to contain stem cell‐like cells called cancer stem cells (CSCs). These cells are endowed with high tumorigenic capacity and may be the cells that drive tumor formation, maintain tumor homeostasis, and mediate tumor metastasis. Since these self‐renewing cancer cells may be the sole population to develop a primary tumor, it is predicted that CSCs may also represent the lethal seeds of metastasis, as supported by a flurry of recent studies on the relationship between CSCs and metastasis. Herein, we summarize current knowledge of stem/progenitor cells and CSCs, especially in the context of normal human prostate and prostate cancer. We further update the recently gained knowledge on the involvement of CSCs in metastasis. We also discuss the fundamental influence of tumor microenvironment on the manifestation of CSCs and metastasis. Finally, we discuss the clinical implication of CSC‐based therapy. J. Surg. Oncol. 2011;103:558–562. © 2011 Wiley‐Liss, Inc.
Perspectives on lymphangiogenesis and angiogenesis in cancer
Authors: Holopainen Tanja , Bry Maija , Alitalo Kari , Saaristo Anne
Published: April 2011

Tumor‐associated neovascularization allows tumor cells to express their critical growth advantage, whereas lymphatic invasion is crucial for the metastatic process. Various growth factors stimulate blood and lymphatic neovascularization and modulate vessel permeability in tumors. The first anti‐angiogenic drugs are already in routine use, and new anti‐vascular therapeutics are evaluated in clinical trials. Conversely, pro‐lymphangiogenic therapy could be implemented to treat cancer survivors suffering from secondary lymphedema. J. Surg. Oncol. 2011;103:484–488. © 2011 Wiley‐Liss, Inc.
Impact of nodal status and tumor burden in sentinel lymph nodes on the clinical outcomes of cancer patients
Authors: Leong Stanley P.L. , Zuber Markus , Ferris Robert L. , Kitagawa Yuko , Cabanas Ramon , Levenback Charles , Faries Mark , Saha Sukamal
Published: April 2011

The validation of sentinel lymph node (SLN) concept in melanoma and breast cancer has established a new paradigm in cancer metastasis that, in general, cancer cells spread in a orderly fashion from the primary site to the SLNs in the regional nodal basin and then to the distant sites. In this review article, we examine the development of SLN concept in penile carcinoma, melanoma and breast carcinoma and its application to other solid cancers with emphasis of the relationship between micrometastasis in SLNs and clinical outcomes. J. Surg. Oncol. 2011;103:518–530. © 2011 Wiley‐Liss, Inc.
Genomic signatures of cancer: Basis for individualized risk assessment, selective staging and therapy
Authors: Baehner Frederick L. , Lee Mark , Demeure Michael J. , Bussey Kimberly J. , Kiefer Jeffrey A. , Barrett Michael T.
Published: April 2011

The development of DNA microarray and quantitative real‐time polymerase chain reaction technologies has allowed for precise quantitation of RNA expression of hundreds to thousands of genes. These technologies have significantly impacted the study and understanding of cancer in terms of its molecular and genetic characteristics. In this review article, breast cancer, colon cancer, and adrenal carcinoma have been chosen to illustrate the principle and techniques of genomic profiling and to illustrate how such methods may be used to develop genomic signatures for personalized risk assessment and to individualize patient treatment. J. Surg. Oncol. 2011;103:563–573. © 2011 Wiley‐Liss, Inc.
Unique patterns of metastases in common and rare types of malignancy
Authors: Leong Stanley P.L. , Nakakura Eric K. , Pollock Raphael , Choti Michael A. , Morton Donald L. , Henner W. David , Lal Anita , Pillai Raji , Clark Orlo H. , Cady Blake
Published: April 2011

This review on the unique patterns of metastases by common and rare types of cancer addresses regional lymphatic metastases but also demonstrates general principles by consideration of vital organ metastases. These general features of successfully treated metastases are relationships to basic biological behavior as illustrated by disease‐free interval, organ‐specific behavior, oligo‐metastatic presentation, genetic control of the metastatic pattern, careful selection of patients for surgical resection, and the necessity of complete resection of the few patients eligible for long‐term survival after resection of vital organ metastasis. Lymph node metastases, while illustrating these general features, are not related to overall survival because lymph node metastases themselves do not destroy a vital organ function, and therefore have no causal relationship to overall survival. When a cancer cell spreads to a regional lymph node, does it also simultaneously spread to the systemic site or sites? Alternatively, does the cancer spread to the regional lymph node first and then it subsequently spreads to the distant site(s) after an incubation period of growth in the lymph node? Of course, if the cancer is in its incubation stage in the lymph node, then removal of the lymph node in the majority of cases with cancer cells may be curative. The data from the sentinel lymph node era, particularly in melanoma and breast cancer, is consistent with the spectrum theory of cancer progression to the sentinel lymph node in the majority of cases prior to distant metastasis. Perhaps, different subsets of cancer may be better defined with relevant biomarkers so that mechanisms of metastasis can be more accurately defined on a molecular and genomic level. J. Surg. Oncol. 2011;103:607–614. © 2011 Wiley‐Liss, Inc.
CyclinD1, p53, E‐cadherin, and VEGF discordant expression in paired regional metastatic lymph nodes of esophageal squamous cell carcinoma: A tissue array analysis
Authors: Luo Kong‐Jia , Hu Yi , Wen Jing , Fu Jian‐Hua
Published: April 2011

Background and Objectives

The correlation of biomarker expression between primary tumors and corresponding metastases has not yet been well reported in esophageal squamous cell carcinoma (ESCC). This study was to confirm whether primary ESCC tumors differ from their regional metastatic lymph nodes (RMLN) in CyclinD1, p53, E‐cadherin, and vascular endothelial growth factor (VEGF) expression and determine prognostic value of their alteration.

Methods

There were 134 patients with stage T3N1‐3M0 ESCC recruited for the research. Expression of CyclinD1, p53, E‐cadherin, and VEGF was evaluated in primary ESCC tumors and their paired RMLN assembled on tissue microarrays by immunohistochemistry (IHC). The comparison of expression in different lesion and their correlation with prognosis was analyzed.

Results

E‐cadherin was discordant expression in 55.2% cases and appeared to be more frequently positive in metastatic lymph nodes (P < 0.001). The VEGF expression level was significantly higher in primary tumors (P < 0.001). Combined analysis of VEGF expressions in paired lesions (P = 0.003) and its decreased expression (P = 0.006) were both predictive.

Conclusions

Biomarker expression was discordant between the primary tumor and its paired lymphatic metastasis in over 25% of patient with ESCC. VEGF discordant expression was a new prognostic factor and combined analysis of expression in paired lesions was useful to predict. Analysis of protein expression only in primary tumors would be inadequate to judge prognosis. J. Surg. Oncol. 2011; 104:236–243. © 2011 Wiley‐Liss, Inc.
Crosslinking of Trimethylene Carbonate and D, L‐Lactide (Co‐) Polymers by Gamma Irradiation in the Presence of Pentaerythritol Triacrylate
Authors: Bat Erhan , van Kooten Theo G. , Feijen Jan , Grijpma Dirk W.
Published: April 2011

High‐molecular‐weight (co)polymers of trimethylene carbonate and D,L‐lactide are efficiently crosslinked using PETA during gamma irradiation. Form‐stable networks with gel contents of 86 ± 5 to 96 ± 1 are obtained from non‐crystalline (co)polymers. Glass transition temperatures and elastic moduli of the networks can be varied by adjusting the copolymer composition. The PETA‐containing (co)polymer networks are not cytotoxic. Upon incubation in macrophage cultures for 14 d, all (co)polymer films and PETA‐containing network films erode to varying extents, showing that these materials can be degraded by cell‐mediated erosion processes. This method is very useful for the facile preparation of TMC‐ and DLLA‐containing form‐stable networks from high‐molecular‐weight polymers.

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Tobacco carcinogen mediated up‐regulation of AP‐1 dependent pro‐angiogenic cytokines in head and neck carcinogenesis
Authors: Swenson Wade G. , Wuertz Beverly R.K. , Ondrey Frank G.
Published: April 2011

Tobacco is notably genotoxic and associated with head and neck carcinogenesis. Cigarette carcinogens have the capacity to alter early response gene expression in tobacco‐related malignancies via genes such as nuclear factor kappa B (NFκB). A number of early response gene activation events are also facilitated by fos/jun activator protein 1 (AP‐1) associated pathways. In the present study, we hypothesize that tobacco products may induce microenvironment alterations, promoting angiogenesis and providing a permissive environment for head and neck cancer progression. In an in vitro analysis, we employed immortalized oral keratinocyte (HOK‐16B) and laryngeal squamous carcinoma (UM‐SCC‐11A) cells to investigate interleukin (IL)‐8 and vascular endothelial growth factor (VEGF) induction by cigarette smoke condensate (CSC). IL‐8 and VEGF expression is based on interactions between NFκB, AP‐1, and NF‐IL6. We identified at least 1.5‐fold dose‐dependent induction of AP‐1, VEGF, and IL‐8 promoter/reporter gene activity after 24 h exposure to CSC. Next, we stably transfected UM‐SCC‐11A cells with A‐Fos, a dominant negative AP‐1 protein. Treatment with CSC of the A‐Fos cell lines compared to empty vector controls significantly down‐regulated AP‐1, VEGF, and IL‐8 promoter/reporter gene expression. We also performed ELISAs and discovered significant up‐regulation of IL‐8 and VEGF secretion by UMSCC 11A after treatment with phorbol 12‐myristate 13‐acetate, tumor necrosis factor alpha, and CSC, which was down‐regulated by the A‐Fos dominant negative protein. We conclude tobacco carcinogens up‐regulate AP‐1 activity and AP‐1 dependent IL‐8 and VEGF gene expression in head and neck cancer. This up‐regulation may promote an angiogenic phenotype favoring invasion in both premalignant and squamous cancer cells of the head and neck. © 2011 Wiley‐Liss, Inc.
Meta‐analysis of 123I‐MIBG cardiac scintigraphy for the diagnosis of Lewy body–related disorders
Authors: King Alisha E. , Mintz Jim , Royall Donald R.
Published: April 2011

Patients with parkinsonism pose a diagnostic challenge. Parkinson's disease may be difficult to distinguish from multiple system atrophy and progressive supranuclear palsy, whereas Parkinson's disease and dementia with Lewy bodies can be difficult to distinguish from Alzheimer's disease and other dementias. A number of studies have found diminished cardiac 123I‐metaiodobenzylguanidine uptake in Lewy body–related conditions (Parkinson's disease and Lewy body dementia). In 2005, the Dementia With Lewy Bodies Consortium considered 123I‐metaiodobenzylguanidine cardiac scintigraphy a “supportive” diagnostic feature, based on limited evidence. We report a meta‐analysis of the literature and an assessment of the utility of 123I‐metaiodobenzylguanidine for the diagnosis of dementia with Lewy bodies and Parkinson's disease. A search was conducted of articles published between 1950 and June 2010. Forty‐six studies involving neuropsychiatric and movement disorders, comprising 2680 subjects, were included in the analysis. A mixed‐effects regression model was used to analyze the delayed mean heart‐to‐mediastinum ratio of 123I‐metaiodobenzylguanidine uptake. 123I‐metaiodobenzylguanidine cardiac scintigraphy sensitively detected and specifically distinguished 2 diagnostic clusters: (1) Parkinson's disease, dementia with Lewy bodies, and rapid eye movement sleep behavior disorder; and (2) normal controls and patients with Alzheimer's disease, multiple system atrophy, progressive supranuclear palsy, vascular dementia, and frontotemporal dementia. The area under the receiver operating characteristic curve was 0.987 at a cluster discriminatory heart‐to‐mediastinum ratio threshold of 1.77. This threshold yielded 94% sensitivity and 91% specificity for the discrimination of these diagnostic clusters. 123I‐metaiodobenzylguanidine cardiac scintigraphy can accurately distinguish between 2 movement disorders, Parkinson's disease and multiple system atrophy, and between 2 common causes of dementia, Alzheimer's disease and dementia with Lewy bodies. © 2011 Movement Disorder Society
Synthesis and characterization of semicrystalline triblockcopolymers of isotactic polystyrene and polydimethylsiloxane
Authors: Gall Barbara T. , Thomann Ralf , Mülhaupt Rolf
Published: April 2011

iPS‐b‐PDMS‐b‐iPS triblock copolymers were prepared by hydrosilylation of vinyl‐terminated isotactic polystyrenes (iPS) with α,ω‐bis(dimethylsilane)‐terminated poly(dimethylsiloxane)s (PDMS). As a function of the molecular weights of the two components, the triblock copolymer composition was varied between 9.0 and 98 wt % iPS. The resulting triblock copolymers remained soluble during block copolymer synthesis due to slow iPS crystallization in solution. At iPS content exceeding 31 wt %, the iPS crystallization was achieved by postpolymerization annealing and melt processing. The triblock copolymers melted above 200 °C with melting temperatures very similar to those of the corresponding iPS homopolymers. Nanostructure and microstructure formation of both amorphous and semicrystalline triblock copolymers were examined by means of light microscopy, atomic force microscopy, and TEM measurements. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
ABC type miktoarm star copolymers through combination of controlled polymerization techniques with thiol‐ene and azide‐alkyne click reactions
Authors: Iskin Birol , Yilmaz Gorkem , Yagci Yusuf
Published: April 2011

ABC type miktoarm star copolymer with polystyrene (PS), poly(ε‐caprolactone) (PCL) and poly(ethylene glycol) (PEG) arms was synthesized using controlled polymerization techniques in combination with thiol‐ene and copper catalyzed azide‐alyne “click” reactions (CuAAC) and characterized. For this purpose, 1‐(allyloxy)‐3‐azidopropan‐2‐ol was synthesized as the core component in a one‐step reaction with high yields (96%). Independently, ω‐thiol functionalized polystyrene (PS‐SH) was synthesized in a two‐step protocol with a very narrow molecular weight distribution. The bromo end function of PS obtained by atom transfer radical polymerization was first converted to xanthate function and then reacted with 1, 2‐ethandithiol to yield desired thiol functional polymer (PS‐SH). The obtained polymer was grafted onto the core by thiol‐ene click chemistry. In the following stage, ε‐caprolactone monomer was polymerized from the core by ring opening polymerization (ROP) using tin octoate as catalyst through hydroxyl groups to form the second arm. Finally, PEG‐acetylene, which was simply synthesized by the esterification of Me‐PEG and 5‐pentynoic acid, was clicked onto the core through azide groups present in the structure. The intermediates at various stages and the final miktoarm star copolymer were characterized by 1H NMR, FTIR, and GPC measurements. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Mesomorphic and conducting properties of dendritic‐linear copolymers via ion‐doped additives
Authors: Choi Jin‐Woo , Cho Byoung‐Ki
Published: April 2011

We studied the conducting and mesomorphic behavior of a dendritic‐linear copolymer on adding hydrophilic additives and lithium salts. For the preparation of the pristine block copolymer (A), a click reaction of a hydrophobic Y‐shaped dendron block and a hydrophilic linear poly(ethylene oxide) coil with Mn = 750 g mol−1 was performed. For ionic block copolymer samples (1–3), a hydrophilic compound (B) bearing two tri(ethylene oxide) chains was used as the additive. In all ionic samples, the lithium concentration per ethylene oxide was chosen to be 0.05. As characterized by polarized optical microscopy and small angle X‐ray scattering techniques, copolymer A showed a hexagonal columnar mesophase. On addition of lithium‐doped additives, ionic samples 1 and 2 with the additive weight fractions (fw) of 10 and 20%, columnar and bicontinuous structures coexisted in the liquid crystalline phase. On the other hand, ionic sample 3 with fw = 30% displayed only a bicontinuous cubic mesophase. Based on the impedance results, with increasing the amount of additives, the conductivity value increased from 3.80 × 10−6 to 2.34 × 10−5 S cm−1 at 35 °C. The conductivity growth could be explained by the interplay of the plasticization effect of the mobile additive and the morphological transformation from 1D to 3D of the ion‐conducting cylindrical cores. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011