bluuebunny/crossref_metadata_2025 huggingface dataset:
Sonographic transvaginal bladder wall thickness: Does the measurement discriminate between urodynamic diagnoses?
Authors: Kuhn Annette , Genoud Sophie , Robinson Dudley , Herrmann Gudrun , Günthert Andreas , Brandner Sonja , Raio Luigi
Published: October 2010

Introduction

Measurement of bladder wall thickness (BWT) using transvaginal ultrasound has previously been shown to discriminate between women with confirmed detrusor overactivity and those with urodynamic stress incontinence. Aim of the current study was to determine if vaginally measured BWT correlates with urodynamic diagnoses in a female population.

Patients and Methods

Between December 2008 and February 2010, adult female consecutive patients undergoing urogynaecologic investigation for lower urinary symptoms were approached to participate in this study. Ethical consent for the current study was obtained. Patients underwent multichannel urodynamics and transvaginal ultrasound measuring the bladder in three location with an emptied bladder.

Results

123 patients were included in the study with a median age of 69 years (range 40–93), median parity of 2 (range 0–3) and a median body mass index of 29.5 kg/m2 (range 23–38). Urodynamic stress incontinence was diagnosed in 59 patients, DO in 40 and obstruction in 24 cases.

Bladder wall thickness was significantly higher in DO patients and in obstruction than in urodynamic stress incontinence.

Detrusor pressure at maximum flow rate (pdet/Qmax) correlated significantly with BWT.

Conclusion

Bladder wall thickness shows a significantly positive correlation to pdet/Qmax and to urodynamic diagnoses of stress incontinence, DO and obstruction. Neurourol. Urodynam. 30:325–328, 2011. © 2010 Wiley‐Liss, Inc.
The molecular background of aggressive B cell lymphomas as a basis for targeted therapy
Authors: de Jong Daphne , Balagué Ponz Olga
Published: October 2010

In contrast to classifications for the majority of solid tumours, non‐Hodgkin's lymphomas have been defined on the basis of their genetic alterations for many years, providing a biologically highly relevant classification. However, for aggressive B cell lymphomas, which unfortunately is the most prevalent group of lymphomas in adults, the stratification is less optimal. Gene expression profiling, analyses of chromosomal alterations and functional assays have been instrumental in dissecting these tumours to support the distinction of essentially different diseases, such as diffuse large B cell lymphoma and Burkitt's lymphoma, and now start to identify the dominant driving oncogenetic pathways that may serve as rational therapeutic targets in this essentially heterogeneous group. In this review, the molecular background and the consequences of the molecular alterations in the context of the consequences for treatment in aggressive B cell lymphoma are discussed. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The molecular pathology of breast cancer progression
Authors: Bombonati Alessandro , Sgroi Dennis C
Published: October 2010

The current model of human breast cancer progression proposes a linear multi‐step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into DCIS and culminates in the potentially lethal stage of invasive ductal carcinoma. For several decades a major challenge to human breast cancer research has been the identification of the molecular alterations associated with the different stages of breast cancer progression. Until recently, progress in attaining this goal has been hampered by technical limitations associated with applying advanced molecular technologies to the microscopic preinvasive stages of breast tumorigenesis. Recent advances in comprehensive, high‐throughput genetic, transcriptomic and epigenetic technologies in combination with advanced microdissection and ex vivo isolation techniques have provided for a more complete understanding of the complex molecular genetic and molecular biological inter‐relationships of the different stages of human breast cancer evolution. Here we review the molecular biological data suggesting that breast cancer develops and evolves along two distinct molecular genetic pathways. We also briefly review gene expression and epigenetic data that support the view of the tumour microenvironment as an important co‐conspirator rather than a passive bystander during human breast tumorigenesis. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Metabolic alterations and targeted therapies in prostate cancer
Authors: Flavin Richard , Zadra Giorgia , Loda Massimo
Published: October 2010

Cancer cells synthesize de novo large amounts of fatty acids and cholesterol, irrespective of the circulating lipid levels and benefit from this increased lipid synthesis in terms of growth advantage, self‐survival and drug resistance. Key lipogenic alterations that commonly occur in prostate cancer include over‐expression of the enzyme fatty acid synthase (FASN) and deregulation of the 5‐AMP‐activated protein kinase (AMPK). FASN is a key metabolic enzyme that catalyses the synthesis of palmitate from the condensation of malonyl‐CoA and acetyl‐CoA de novo and plays a central role in energy homeostasis, by converting excess carbon intake into fatty acids for storage. AMPK functions as a central metabolic switch that governs glucose and lipid metabolism. Recent interest has focused on the potential of targeting metabolic pathways that may be altered during prostate tumorigenesis and progression. Several small molecule inhibitors of FASN have now been described or in development for therapeutic use; in addition, drugs that directly or indirectly induce AMPK activation have potential benefit in prostate cancer prevention and treatment. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Objective assessment of lymphatic and blood vascular invasion in lymph node‐negative breast carcinoma: findings from a large case series with long‐term follow‐up
Authors: Mohammed Rabab AA , Martin Stewart G , Mahmmod Ali M , Macmillan R. Douglas , Green Andrew R , Paish Emma C , Ellis Ian O
Published: October 2010

In a previous study on a small series of breast cancers, we developed objective methods for the assessment of vascular invasion (VI), using immunohistochemical staining. We found that VI was predominantly lymphovascular invasion (LVI), with minimal contribution of blood vascular invasion (BVI). The aims of the current study were: (a) to assess the frequency, extent and prognostic role of LVI and BVI in a large, well‐characterized series of LN‐negative breast cancers; and (b) to assess the ability of VI to stratify early breast cancer into different prognostic groups. Paraffin‐embedded sections from 1005 lymph‐node (LN)‐negative primary invasive breast cancers were stained for CD34, CD31 and podoplanin/D240 to detect BVI and LVI. VI lesions were assessed and the results were correlated with clinicopathological criteria and survival. VI was detected in 218 (22%); 211/218 (97%) were LVI, while BVI was detected in 7/218 (3%). The frequency of LVIs/section ranged from 1 to 79, with no significant difference between the frequency of LVI and outcome. The presence of LVI was significantly associated with adverse disease‐free interval (DFI) and poor overall survival (OS) in both univariate and multivariate analyses. The results from the study indicated that VI in early stage breast cancer is predominantly LVI and that its objective assessment is a powerful independent prognostic factor. Efforts to detect early metastatic activity, such as diligent pathological examination of sentinel LN biopsies would be complimented by the objective evaluation of VI status of the primary tumour. VI status should be included routinely in breast cancer staging systems. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells
Authors: Xu Jing Da , Cao Xi Xi , Long Zi Wen , Liu Xiu Ping , Furuya Tomoko , Xu Jia Wen , Liu Xiao Li , De Xu Zu , Sasaki Kohsuke , Li Qing Quan
Published: October 2010

The reason for and consequences of BCL2L10 down‐regulation in gastric carcinoma are poorly understood. Our aim was to investigate the function of the protein BCL2L10 in gastric carcinoma. We investigated BCL2L10 expression using quantitative real‐time PCR and immunoblotting. The methylation status of the BCL2L10 gene promoter was examined by bisulphite sequencing in fresh gastric normal and carcinoma tissues. We studied apoptosis and proliferation regulation in gastric cancer cell lines using flow cytometry, fluorescence staining, murine xenografting and immunoblotting. Pathway inhibitors were applied to confirm the major pathways involved in apoptosis or proliferation regulation. We observed significant correlations between lower BCL2L10 expression and CpG island hypermethylation of the BCL2L10 gene promoter in gastric carcinoma, apoptosis induced by over‐expressed BCL2L10 through mitochondrial pathways, and proliferation accelerated by BCL2L10 siRNA via the PI3K–Akt signalling pathway in gastric cancer cell lines. The pro‐apoptotic effect of BCL2L10 and growth promotion by BCL2L10 siRNA in gastric cancer cells suggest that it may be a tumour suppressor. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A radiotherapy planning study of RapidArc, intensity modulated radiotherapy, three‐dimensional conformal radiotherapy, and parallel opposed beams in the treatment of pediatric retroperitoneal tumors
Authors: Shaffer Richard , Vollans Emily , Vellani Rosie , Welsh Margaret , Moiseenko Vitali , Goddard Karen
Published: October 2010

Background

This planning study compared RapidArc, fixed‐field IMRT (cIMRT), 3D conformal radiotherapy (3D‐CRT), and a parallel‐opposed pair (POP) for children with retroperitoneal tumors.

Procedure

Plans were generated in eight patients to treat the PTV (dose range 19.8–45 Gy) while limiting kidney and liver doses. In selected patients, vertebral body (VB) dose heterogeneity was minimized. Cumulative DVH parameters, monitor units (MU), and treatment times were compared for the four techniques using the Wilcoxon matched pairs test.

Results

RapidArc and cIMRT covered target volumes more conformally than 3D‐CRT and POP (P = 0.012). There was no difference in the ability to meet kidney dose constraints. A significantly lower volume of the liver received 12 Gy with cIMRT or RapidArc compared with 3D‐CRT (P = 0.028). Where VB was included in PTV, VB dose homogeneity was generally within 94–104% of the prescription dose. Time to deliver a single fraction with RapidArc, POP, 3D‐CRT, and cIMRT was 1.25 ± 0.01, 1.38 ± 0.10, 2.6 ± 0.45, and 4.02 ± 1.12 min, respectively (P = 0.012). Monitor units for a single fraction with POP, 3D‐CRT, RapidArc, and cIMRT were 203 ± 26, 235 ± 32, 325 ± 71, and 665 ± 215, respectively (P < 0.05).

Conclusions

POP resulted in favorable MU, treatment time and dosimetry but had poor conformality. 3D‐CRT was more conformal but had higher MU and treatment time. RapidArc and cIMRT were generally no better dosimetrically than conformal techniques. RapidArc was dosimetrically very similar to cIMRT, but resulted in a major reduction in time and MU used to deliver the radiation. Pediatr Blood Cancer. 2010;56:16–23. © 2010 Wiley‐Liss, Inc.
High reticulocyte count is an independent risk factor for cerebrovascular disease in children with sickle cell anemia
Authors: Silva Célia Maria , Giovani Poliana , Viana Marcos Borato
Published: October 2010

Background

Transcranial Doppler ultrasonography (TCD) is an important way of detecting risk of ischemic stroke in children with sickle cell anemia.

Procedure

A random sample of 262 FS‐hemoglobin children from a newborn screening inception cohort in Brazil (1998–2005) was followed up to May 2009. Pulsed TCD followed STOP protocol. Children with mean blood flow velocity <170 cm/sec in cerebral arteries were classified as low risk; between 170 and 184, low conditional risk; between 185 and 199, high conditional risk; and ≥200, high risk.

Results

Median age, 6.2 years (2–11.2 years); 147 female; 13 children (5%) had ischemic stroke prior to TCD; 186/249 (74.7%) were classified as low risk; 19 (7.6%) as low conditional; 7 (2.8%) as high conditional; and 8 (3.2%) as high risk; inadequate tests, 11.6%. The probability of ischemic stroke at 10 years was 8.3% (SEM 2.3%); of stroke or high‐risk TCD 15.6% (3.5%). Children with stroke or altered TCD (conditional and high risk) were compared to children with normal examinations. They were younger (P = 0.03), with lower hemoglobin (P = 0.003), higher leukocytosis (P = 0.015), and higher reticulocytosis (P < 0.001). Episodes per year of acute chest syndrome were also higher in that group, but not significantly (P = 0.09). Reticulocytosis remained the only significant variable upon multivariate analysis (P = 0.004). Basilar and middle cerebral artery velocities were significantly correlated (R = 0.55; P < 0.001).

Conclusions

Probability of stroke was similar to international reports; of belonging to high‐risk group, lower. High‐reticulocyte count was the most important factor associated with cerebrovascular disease. Basilar artery velocity >130 cm/sec seems to be an indirect sign of an underlying cerebrovascular disease. Pediatr Blood Cancer. 2010;56:116–121. © 2010 Wiley‐Liss, Inc.
Cancer at ages 15–29 years: The contrasting incidence in India and England
Authors: Arora Ramandeep S. , Alston Robert D. , Eden Tim O.B. , Moran Anthony , Geraci Marco , O'Hara Catherine , Birch Jillian M.
Published: October 2010

Background

There has been a steady increase in published research from Europe and North America on the epidemiology of cancers in young people. There are limited data from the developing world. We contrast the incidence of cancer at ages 15–29 years in India and England.

Procedure

Malignant neoplasms in those aged 15–29 years registered during 2001–2003 in five urban population‐based cancer registries (PBCRs) of India and in eight PBCRs in England were included. Site‐based classification was used. Age‐standardized incidence rates were expressed per 100,000 person years.

Results

In India, 4,864 (5.8%) of 84,450 cases and in England, 8,137 (1.2%) of 65,6752 cancer cases occurred in those aged 15–29 years. For this age group, the incidence rate for males and females in India were 12.91 and 14.19, and in England were 27.75 and 28.88, respectively. In males aged 15–29 years, the three most common cancers in India were leukemia, lymphoma, and central nervous system tumors and in England were cancers of male genital organs, lymphoma, and leukemia. Cancers of female genital organs, breast, and leukemia were most common in females in India and cancers of female genital organs, lymphoma, and melanoma in England. For cancers of mouth, stomach, and gall bladder, the incidence was higher in India.

Conclusion

Incidence of cancer at ages 15–29 years in England is higher at most sites than in India. Variation in environmental exposures between the two countries might be an explanation. Under‐ascertainment of cases and gender bias in seeking healthcare may also influence reported incidence rates in India. Pediatr Blood Cancer 2012; 58: 55–60. © 2010 Wiley Periodicals, Inc.
Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis
Authors: Mizukawa Benjamin , George Alex , Pushkaran Suvarnamala , Weckbach Lana , Kalinyak KarenAnn , Heubi James E. , Kalfa Theodosia A.
Published: October 2010

We report a novel glucose‐6‐phosphate dehydrogenase (G6PD) mutation, which we propose to name G6PD Cincinnati (c.1037A > T, p.N346I), found in combination with G6PD Gastonia (c.637G > T, p.V213L) in an infant who presented with neonatal cholestasis. The G6PD Cincinnati mutation results in a non‐conservative amino acid substitution at the tetramer interface disturbing its formation, as seen by native gel electrophoresis and immunoblotting. G6PD Gastonia disrupts dimerization of the enzyme and by itself causes chronic non‐spherocytic hemolytic anemia. The G6PD Cincinnati mutation may have aggravated the clinical picture of G6PD Gastonia with the result of severe perinatal hemolysis causing cholestasis and associated liver injury. Pediatr Blood Cancer 2011;56:840–842. © 2011 Wiley‐Liss, Inc.
Ambulatory high‐dose methotrexate administration among pediatric osteosarcoma patients in an urban, underserved setting is feasible, safe, and cost‐effective
Authors: Mahadeo Kris M. , Santizo Ruth , Baker Lindsay , Curry Joan O'Hanlon , Gorlick Richard , Levy Adam S.
Published: October 2010

Background

We describe the safety, feasibility, and provide a cost‐estimate of outpatient high‐dose methotrexate administration (HDMTX) among an urban, underserved population.

Procedure

A retrospective analysis of ambulatory HDMTX administration among osteosarcoma patients, at Montefiore Medical Center's Children's Hospital (Bronx, NY) was performed. HDMTX (12 g/m2) was given intravenously (IV) over 4 hr after urine alkalinization. Patients were discharged home to continue IV hydration and alkalinization delivered via a home infusion pump. Families were instructed to monitor urine pH overnight and management was adjusted according to our institution's treatment algorithm until MTX level ≤0.1 µmol/L. A cost estimate was performed to assess the difference in costs for outpatient versus hypothetical inpatient administrations.

Results

Of the 97 ambulatory HDMTX administrations, 99% were successfully completed. One patient failed outpatient administration secondary to home infusion pump malfunction. This patient successfully completed subsequent courses as an outpatient. Most patients (72%) had a MTX level of <10 µmol/L at 24 hr post‐HDMTX. No patients were found to have a MTX level of >50 µmol/L at 24 hr. About 26% of courses were associated with grade III or IV neutropenia, 4% were associated with grade III or IV thrombocytopenia and 1% were associated with grade III/IV leukopenia. Compared to a hypothetical hospital inpatient stay, the hospital costs for ambulatory HDMTX were an average of $1400 less per cycle.

Conclusion

Ambulatory HDMTX administration among an underserved, urban population is safe, feasible, and cost‐effective. Pediatr Blood Cancer. 2010;55:1296–1299. © 2010 Wiley‐Liss, Inc.
Recurrent pure CNS germinoma with markedly elevated serum and cerebrospinal fluid human chorionic gonadotropin‐beta (HCGβ)
Authors: Khatua Soumen , Phillips Andrew , Fangusaro Jason , Bovan Sally , Dhall Girish , Finlay Jonathan L.
Published: October 2010

Controversy continues regarding what level of serum and/or cerebrospinal fluid (CSF) human chorionic gonadotrophin‐beta (HCGβ) is consistent with pure germinoma of the central nervous system (CNS). We report a 10‐year female with biopsy‐proven pure germinoma and normal serum and CSF HCGβ who experienced subsequent biopsy‐proven recurrences of germinoma. At recurrence, serum and CSF HCGβ levels were 560 and 3,202 mIU/ml, respectively, although final autopsy demonstrated pure germinoma. This case illustrates the need to re‐evaluate the assumption that pathologically pure germinomas may be associated with high levels of HCGβ which are unrelated to nongerminomatous germ cell tumor (NGGCT)/choriocarcinomatous elements. Pediatr Blood Cancer 2011;56:863–864. © 2011 Wiley‐Liss, Inc.
Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus
Authors: Weill Alain , Païta Michel , Tuppin Philippe , Fagot Jean‐Paul , Neumann Anke , Simon Dominique , Ricordeau Philippe , Montastruc Jean‐Louis , Allemand Hubert
Published: October 2010

Purpose

To evaluate and quantify in diabetic patients treated with benfluorex in France, a fenfluramine‐derivated product, a possible increase in risk of valvular heart disease, previously suggested by several published case reports.

Methods

This was a French comparative cohort study using data from two large national linked databases, health insurance system (SNIIRAM) and hospitalization (PMSI). Patients aged 40–69 years with reimbursement for oral antidiabetic and/or insulin in 2006 were eligible. Exposed patients were defined as patients with at least one benfluorex reimbursement in 2006. Selected admission diagnoses of interest in 2007 and 2008 PMSI databases were valvular insufficiency for any cause, mitral insufficiency, aortic insufficiency, and valvular replacement surgery with cardiopulmonary bypass. Relative risks (RR) were adjusted on gender, age, and history of chronic cardiovascular disease.

Results

A total of 1 048 173 diabetic patients were included, with 43 044 (4.1%) exposed to benfluorex. The risk of hospitalization in 2007 and 2008 for any cardiac valvular insufficiency was higher in the benfluorex group: crude RR = 2.9 [95% confidence interval 2.2–3.7] and adjusted RR = 3.1 [2.4–4.0], with a lower risk for patients with lower cumulative dose of benfluorex. Adjusted RR for mitral insufficiency and aortic insufficiency admissions were 2.5 [1.9–3.7] and 4.4 [3.0–6.6], respectively. Adjusted RR for valvular replacement surgery was 3.9 [2.6–6.1].

Conclusions

Benfluorex in diabetic patients was significantly associated with hospitalization for valvular heart disease in the 2 years following benfluorex exposure. Linkage between SNIIRAM and PMSI databases is in France a valuable tool to quantify the risk of serious adverse drug reactions. Copyright © 2010 John Wiley & Sons, Ltd.
Methods for drug safety signal detection in longitudinal observational databases: LGPS and LEOPARD
Authors: Schuemie Martijn J.
Published: October 2010

Purpose

There is a growing interest in using longitudinal observational databases for drug safety signal detection, but most of the existing statistical methods are tailored towards spontaneous reporting. Here a sequential set of methods for detecting and filtering drug safety signals in longitudinal databases is presented.

Method

Longitudinal GPS (LGPS) is a modification of the Gamma Poisson Shrinker (GPS) that uses person time rather than case counts for the estimation of the expected number of events. Longitudinal Evaluation of Observational Profiles of Adverse events Related to Drugs (LEOPARD) is a method that can be used to automatically discard false drug‐event associations caused by protopathic bias or misclassification of the dates of the adverse events by comparing prior event prescription rates to post event prescription rates. LEOPARD can generate a single test statistic, or a visualization that can be used for more qualitative information on the relationship between drug and event. Both methods were evaluated using data simulated using the Observational medical dataset SIMulator (OSIM), including the dataset used in the Observational Medical Outcomes Partnership (OMOP) cup, a recent public competition for signal detection methods. The Mean Average Precision (MAP) was used for performance measurement.

Results

On the OMOP cup data, LGPS achieved a MAP of 0.245, and the combination of LGPS and LEOPARD achieved a MAP of 0.260, the highest score in the competition.

Conclusions

The sequential use of LGPS and LEOPARD have proven to be a useful novel set of methods for drug safety signal detection on longitudinal health records. Copyright © 2010 John Wiley & Sons, Ltd.
Multi‐responsive hydrogels based on N‐isopropylacrylamide and sodium alginate
Authors: Dumitriu Raluca P , Mitchell Geoffrey R , Vasile Cornelia
Published: October 2010

Hydrogels consisting of sodium alginate and N‐isopropylacrylamide covalently crosslinked with N,N′‐methylenebisacrylamide were prepared. The mixed‐interpenetrated networks obtained were characterized using elemental analysis, Fourier transform infrared and Raman spectroscopy, swelling measurements and environmental scanning electron microscopy. The thermo‐ and pH‐responsive properties of these hydrogels were evidenced by their swelling behaviour, which depended also on the amount of crosslinking agent and hydrogel composition. Copyright © 2010 Society of Chemical Industry
Synthesis and properties of copolymers of poly(ether ketone ketone) and poly(ether amide ether amide ether ketone ketone)
Authors: Jiang Jianwen , Ding Nengwen , Cai Mingzhong
Published: October 2010

Poly(aryl ether ketone)s (PAEKs) are a class of high‐performance engineering thermoplastics known for their excellent combination of chemical, physical and mechanical properties, and the synthesis of semicrystalline PAEKs with increased glass transition temperatures (Tg) is of much interest. In the work reported, a series of novel copolymers of poly(ether ketone ketone) (PEKK) and poly(ether amide ether amide ether ketone ketone) were synthesized by electrophilic solution polycondensation of terephthaloyl chloride with a mixture of diphenyl ether and N,N′‐bis(4‐phenoxybenzoyl)‐4,4′‐diaminodiphenyl ether (BPBDAE) under mild conditions. The copolymers obtained were characterized using various physicochemical techniques. The copolymers with 10–35 mol% BPBDAE are semicrystalline and have markedly increased Tg over commercially available poly(ether ether ketone) and PEKK due to the incorporation of amide linkages in the main chain. The copolymers with 30–35 mol% BPBDAE not only have high Tg of 178–186 °C, but also moderate melting temperatures of 335–339 °C, having good potential for melt processing. The copolymers with 30–35 mol% BPBDAE have tensile strengths of 102.4–103.8 MPa, Young's moduli of 2.33–2.45 GPa and elongations at break of 11.7–13.2%, and exhibit high thermal stability and good resistance to organic solvents. Copyright © 2010 Society of Chemical Industry
Preparation and characterization of light‐cured methacrylate/montmorillonite nanocomposites
Authors: Mucci Verónica , Pérez Javier , Vallo Claudia I
Published: October 2010

Polymer/clay nanocomposites were prepared from dimethacrylate monomers, commonly used in dental restorative resins, and an organically modified silicate (montmorillonite). The photopolymerization process was hardly affected by the presence of the silicate filler, and thus 2 mm thick samples containing 3 wt% clay were extensively cured. Transmission electron microscopy revealed that the montmorillonite platelets were either intercalated or exfoliated. Nevertheless, for all formulations, intermediate‐sized aggregates of about 1 µm were present and their fraction increased as the amount of filler increased. The presence of the clay was found to have no major effect on the flexural modulus and compressive yield strength of the nanocomposites. Moreover, the water uptake of nanocomposites containing 3 wt% clay was about 10–15% higher than that of unfilled monomers. Modification of the clay surface with alternative organic cations is certainly necessary in order to achieve an optimal dispersion of the clay in the polymer matrix. Copyright © 2010 Society of Chemical Industry
Recent developments in fuel‐processing and proton‐exchange membranes for fuel cells
Authors: Bai He , Ho WS Winston
Published: October 2010

In recent years, great progress has been made in the development of proton‐exchange membrane fuel cells (PEMFCs) for both mobile and stationary applications. This review covers two types of new membranes: (1) carbon dioxide‐selective membranes for hydrogen purification and (2) proton‐exchange membranes; both of these are crucial to the widespread application of PEMFCs. On hydrogen purification for fuel cells, the new facilitated transport membranes synthesized from incorporating amino groups in polymer networks have shown high CO2 permeability and selectivity versus H2. The membranes can be used in fuel processing to produce high‐purity hydrogen (with less than 10 ppm CO and 10 ppb H2S) for fuel cells. On proton‐exchange membranes, the new sulfonated polybenzimidazole copolymer‐based membranes can outperform Nafion® under various conditions, particularly at high temperatures and low relative humidities. Copyright © 2010 Society of Chemical Industry
A systems biology analysis of metastatic melanoma using in‐depth three‐dimensional protein profiling
Authors: Han Mee‐Jung , Wang Huan , Beer Lynn A. , Tang Hsin‐Yao , Herlyn Meenhard , Speicher David W.
Published: October 2010

Melanoma is an excellent model to study molecular mechanisms of tumor progression because melanoma usually develops through a series of architecturally and phenotypically distinct stages that are progressively more aggressive, culminating in highly metastatic cells. In this study, we used an in‐depth, 3‐D protein level, comparative proteome analysis of two genetically, very closely related melanoma cell lines with low‐ and high‐metastatic potentials to identify proteins and key pathways involved in tumor progression. This proteome comparison utilized fluorescent tagging of cell lysates followed by microscale solution IEF prefractionation and subsequent analysis of each fraction on narrow‐range 2‐D gels. LC‐MS/MS analysis of gel spots exhibiting significant abundance changes identified 110 unique proteins. The majority of observed abundance changes closely correlate with biological processes central to cancer progression, such as cell death and growth and tumorigenesis. In addition, the vast majority of protein changes mapped to six cellular networks, which included known oncogenes (JNK, c‐myc, and N‐myc) and tumor suppressor genes (p53 and transforming growth factor‐β) as critical components. These six networks showed substantial connectivity, and most of the major biological functions associated with these pathways are involved in tumor progression. These results provide novel insights into cellular pathways implicated in melanoma metastasis.
Proteomic analysis of intestinal ischemia/reperfusion injury and ischemic preconditioning in rats reveals the protective role of aldose reductase
Authors: Liu Ke‐Xuan , Li Cai , Li Yun‐Sheng , Yuan Bao‐long , Xu Miao , Xia Zhengyuan , Huang Wen‐Qi
Published: October 2010

Intestinal ischemia/reperfusion (I/R) injury is a critical condition associated with high morbidity and mortality. Studies show that ischemic preconditioning (IPC) can protect the intestine from I/R injury. However, the underlying molecular mechanisms of this event have not been fully elucidated. In the present study, 2‐DE combined with MALDI‐MS was employed to analyze intestinal mucosa proteomes of rat subjected to I/R injury in the absence or presence of IPC pretreatment. The protein content of 16 proteins in the intestinal mucosa changed more than 1.5‐fold following intestinal I/R. These proteins were, respectively, involved in the cellular processes of energy metabolism, anti‐oxidation and anti‐apoptosis. One of these proteins, aldose reductase (AR), removes reactive oxygen species. In support of the 2‐DE results, the mRNA and protein expressions of AR were significantly downregulated upon I/R injury and enhanced by IPC as confirmed by RT‐PCR and western blot analysis. Further study showed that AR‐selective inhibitor epalrestat totally turned over the protective effect of IPC, indicating that IPC confers protection against intestinal I/R injury primarily by increasing intestinal AR expression. The finding that AR may play a key in intestinal ischemic protection might offer evidences to foster the development of new therapies against intestinal I/R injury.
Proteomics and systems biology to tackle biological complexity: Yeast as a case study
Authors: Alberghina Lilia , Cirulli Claudia
Published: October 2010

In this note we discuss how, by using budding yeast as model organism (as has been done in the past for biochemical, genetics and genomic studies), the integration of “omics” sciences and more specifically of proteomics with systems biology offers a very profitable approach to elucidating regulatory circuits of complex biological functions.
Proteomic analysis of the outer membrane of Protochlamydia amoebophila elementary bodies
Authors: Heinz Eva , Pichler Peter , Heinz Christian , op den Camp Huub J. M. , Toenshoff Elena Rebecca , Ammerer Gustav , Mechtler Karl , Wagner Michael , Horn Matthias
Published: October 2010

Chlamydiae are obligate intracellular bacteria, comprising some of the most important bacterial pathogens of animals and humans. During their unique developmental cycle they have to attach to and enter their eukaryotic host cells, a process mediated by proteins in the chlamydial outer membrane. So far the only experimental data for chlamydial outer membrane proteins are available from members of the Chlamydiaceae, a family comprising exclusively human and animal pathogens. To get further insights into the evolution of the protein composition of the chlamydial outer membrane and into host‐dependent differences, we performed an extensive experimental analysis of outer membrane fractions of Protochlamydia amoebophila elementary bodies, which constitute the infectious form of this non‐pathogenic member of the Chlamydiae that thrives as a symbiont in Acanthamoeba spp. We used 1‐D and 2‐DE in combination with MALDI‐TOF, MALDI‐TOF/TOF and nanoLC‐ESI‐MS/MS, and compared our experimental results with a previously published in silico analysis of chlamydial outer membrane proteins. This resulted in the identification of 38 proteins supported by both studies and therefore very likely to be located in the P. amoebophila outer membrane. The obtained experimental data provide the first comprehensive overview of outer membrane proteins of a chlamydial organism outside the Chlamydiaceae. They reveal both fundamental differences and convergent evolution between pathogenic and symbiotic chlamydiae.
2‐D DIGE analysis of the budding yeast pH 6–11 proteome in meiosis
Authors: Scaife Caitriona , Mowlds Peter , Grassl Julia , Polden Julie , Daly Catherine N. , Wynne Kieran , Dunn Michael J. , Clyne Rosemary K.
Published: October 2010

Meiosis is the cell division that generates haploid gametes from diploid precursors. To provide insight into the functional proteome of budding yeast during meiosis, a 2‐D DIGE kinetic approach was used to study proteins in the pH 6–11 range. Nearly 600 protein spots were visualised and 79 spots exhibited statistically significant changes in abundance as cells progressed through meiosis. Expression changes of up to 41‐fold were detected and protein sequence information was obtained for 48 spots. Single protein identifications were obtained for 21 spots including different gel mobility forms of 5 proteins. A large number of post‐translational events are suggested for these proteins, including processing, modification and import. The data are incorporated into an online 2‐DE map of meiotic proteins in budding yeast, which extends our initial DIGE investigation of proteins in the pH 4–7 range. Together, the analyses provide peptide sequence data for 84 protein spots, including 50 single‐protein identifications and gel mobility isoforms of 8 proteins. The largest classes of identified proteins include carbon metabolism, protein catabolism, protein folding, protein synthesis and the oxidative stress response. A number of the corresponding genes are required for yeast meiosis and recent studies have identified similar classes of proteins expressed during mammalian meiosis. This proteomic investigation and the resulting protein reference map make an important contribution towards a more detailed molecular view of yeast meiosis.
Structural and thermodynamic analysis of the GFP:GFP‐nanobody complex
Authors: Kubala Marta H. , Kovtun Oleksiy , Alexandrov Kirill , Collins Brett M.
Published: October 2010

The green fluorescent protein (GFP)‐nanobody is a single‐chain VHH antibody domain developed with specific binding activity against GFP and is emerging as a powerful tool for isolation and cellular engineering of fluorescent protein fusions in many different fields of biological research. Using X‐ray crystallography and isothermal titration calorimetry, we determine the molecular details of GFP:GFP‐nanobody complex formation and explain the basis of high affinity and at the same time high specificity of protein binding. Although the GFP‐nanobody can also bind YFP, it cannot bind the closely related CFP or other fluorescent proteins from the mFruit series. CFP differs from GFP only within the central chromophore and at one surface amino acid position, which lies in the binding interface. Using this information, we have engineered a CFP variant (I146N) that is also able to bind the GFP‐nanobody with high affinity, thus extending the toolbox of genetically encoded fluorescent probes that can be isolated using the GFP‐nanobody.
Androgen hypersensitivity in prostate cancer: Molecular perspectives on androgen deprivation therapy strategies
Authors: Foley Ruth , Marignol Laure , Keane John P. , Lynch Thomas H. , Hollywood Donal
Published: October 2010

Androgen deprivation therapy is initially successful in treating advanced prostate cancer. However, after a period of time tumors inevitably recur. Improved understanding of the various biochemical causes of resistance to hormonal therapy is of crucial importance for developing more effective therapeutic strategies in this cohort of patients. This review discusses the preclinical evidence for androgen hypersensitivity (AH), as a mechanism by which tumors become hormone‐refractory (HR). We propose that the growth of some such tumors may be not only stimulated by, but also dependent on low hormone levels, and furthermore, that normal hormone concentrations can have an inhibitory effect on growth. The incidence and importance of AH merits further investigation both in preclinical studies and during clinical trials of intermittent androgen withdrawal or testosterone replacement. We suggest that a subset of HR prostate cancer patients who have androgen‐hypersensitive tumors could be particularly amenable to these treatments. Finally, potential approaches for developing biomarkers to identify such patients are explored. Prostate 77:550–557, 2011. © 2010 Wiley‐Liss, Inc.
Effective targeting of prostate cancer by lymphocytes redirected by a PSMA × CD3 bispecific single‐chain diabody
Authors: Fortmüller Kerstin , Alt Karen , Gierschner Dorothee , Wolf Philipp , Baum Volker , Freudenberg Nikolaus , Wetterauer Ulrich , Elsässer‐Beile Ursula , Bühler Patrick
Published: October 2010

BACKGROUND

For redirecting T‐lymphocytes to induce prostate cancer cell lysis, we constructed a novel bispecific single‐chain (bsc) diabody directed to the prostate specific membrane antigen (PSMA) and the T‐cell receptor (TCR)‐associated CD3 molecule on T‐cells.

METHODS

The PSMA × CD3 bsc diabody was generated from an anti‐CD3 single chain Fv fragment (scFv) and the anti‐PSMA scFv D7. It was expressed in E. coli and purified from the periplasmic extract and culture supernatant by immobilized metal affinity chromatography (IMAC). The binding properties were tested on PSMA‐expressing prostate cancer cells and PSMA‐negative cell lines as well as on Jurkat cells by flow cytometry. For in vitro functional analysis, a cell viability test (WST‐1) was used and activation of T‐cells was determined by measuring the surface marker expression of CD25 and CD69. For in vivo evaluation, the diabody was administered in combination with human peripheral blood lymphocytes (Ly) in a C4‐2 xenograft‐SCID mouse model.

RESULTS

Specific binding of the PSMA × CD3 bsc diabody both to CD3‐positive Jurkat cells and PSMA‐expressing C4‐2 cells was shown by flow cytometry. In vitro, the PSMA × CD3 bsc diabody proved to be a potent agent for retargeting CD4+ and CD8+ human lymphocytes to lyse C4‐2 prostate cancer cells. Treatment of SCID mice bearing C4‐2 tumor xenografts with the diabody and human lymphocytes efficiently inhibited tumor growth.

CONCLUSIONS

The PSMA × CD3 bsc diabody bears a high potential for the immunotherapy of prostate cancer. Prostate 71:588–596, 2011. © 2010 Wiley‐Liss, Inc.
Internal prostatic architecture on transrectal ultrasonography predicts future prostatic growth: Natural history of prostatic hyperplasia in a 15‐year longitudinal community‐based study
Authors: Fukuta Fumimasa , Masumori Naoya , Mori Mitsuru , Tsukamoto Taiji
Published: October 2010

BACKGROUND

From 1992 to 1993, we conducted a cross‐sectional community‐based study to clarify the prevalence of benign prostatic hyperplasia in Japanese men aged 40–79. Based on the results, we hypothesized that the internal prostatic architecture (IPA) on transrectal ultrasonography (TRUS) would predict future prostatic growth. We investigated the changes in prostate volume (PV) over time and validated our hypothesis on predictors for future prostatic growth.

METHODS

Of 319 participants in the initial study, the PV of 104 men was evaluated by TRUS with approximately a 15‐year follow‐up in the current study. We categorized prostates into three groups based on the IPA: group 1, invisible transition zone (TZ); group 2, visible TZ with an unclear border; and group 3, visible TZ with a clear border.

RESULTS

Overall PV significantly increased from 17.4 ml to 23.9 ml (P < 0.001). The median PV changes by age decade (40s, 50s, 60s, and 70s) were 5.5, 5.6, 8.6, and 11.1 ml, respectively. Those by baseline PV <20 ml, 20–25 ml, and ≥25 ml were 5.3, 9.8, and 14.7 ml, respectively. Those by baseline IPA for group 1, group 2, and group 3 were 4.7, 6.5, and 17.3 ml, respectively. Multiple linear regression analysis indicated that PV (P = 0.027) and the IPA (P < 0.001) at baseline were independent predictors for future prostatic growth.

CONCLUSIONS

This was the first study by longitudinal community‐based study that the PV in Japanese men increased during 15 years. The IPA on TRUS is useful for predicting future prostatic growth. Prostate 71:597–603, 2011. © 2010 Wiley‐Liss, Inc.
Androgen regulation of micro‐RNAs in prostate cancer
Authors: Waltering Kati K. , Porkka Kati P. , Jalava Sanni E. , Urbanucci Alfonso , Kohonen Pekka J. , Latonen Leena M. , Kallioniemi Olli P. , Jenster Guido , Visakorpi Tapio
Published: October 2010

BACKGROUND

Androgens play a critical role in the growth of both androgen dependent and castration‐resistant prostate cancer (CRPC). Only a few micro‐RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs.

METHODS

We utilized LNCaP derived model, we have established, and which overexpresses the androgen receptor (AR), the VCaP cell line, and 13 intact‐castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT‐PCR (Q‐RT‐PCR). Transfection of pre‐miR‐141 and anti‐miR‐141 was also used.

RESULTS

Seventeen miRNAs were >1.5‐fold up‐ or downregulated upon dihydrotestosterone (DHT) treatment in the cell lines, and 42 after castration in the AR‐positive xenografts. Only four miRNAs (miR‐10a, miR‐141, miR‐150*, and miR‐1225‐5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR‐141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR‐141 enhanced growth of parental LNCaP cells while inhibition of miR‐141 by anti‐miR‐141 suppressed the growth of the LNCaP subline overexpressing AR.

CONCLUSIONS

Only a few miRNAs were found to be androgen‐regulated in both cell lines and xenografts models. Of those, the expression of miR‐141 was upregulated in cancer. The ectopic overexpression of miR‐141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC. Prostate 71:604–614, 2011. © 2010 Wiley‐Liss, Inc.
A role for class 3 semaphorins in prostate cancer
Authors: Blanc V. , Nariculam J. , Munson P. , Freeman A. , Klocker H. , Masters J. , Williamson M.
Published: October 2010

BACKGROUND

Class 3 semaphorins are secreted proteins that act as guidance cues for migrating cells via their transmembrane receptors plexins and neuropilins. Semaphorins have a role in cancer affecting tumor progression both directly, and indirectly by affecting angiogenesis.

METHODS

The expression of semaphorins and their receptors in prostate cancer cell lines and tissue was determined by RT‐PCR, Western blotting and immunohistochemistry. The effect of Sema3E on prostate cancer cell lines was determined by adhesion assays and transwell migration assays.

RESULTS

Semaphorins and their receptors, plexins and neuropilins, are widely co‐expressed in prostate cancer cell lines and tissue with a significant overexpression of Sema3E in tumor tissue. Sema3E affected integrin‐mediated adhesion to fibronectin of prostate cancer cells, and inhibited their motility. Expression of Sema3C was upregulated and Sema3A and Sema3E were down regulated in prostate cells by hypoxia, consistent with an additional role for Sema3A and 3E as anti‐angiogenic factors in prostate cancer.

CONCLUSIONS

Semaphorin 3E is aberrantly expressed in prostate cancer and affects adhesion and motility of prostate cancer cells, indicating a role for the Sema3E/PlexinD1 signaling pathway in prostate cancer and identifying a new possible target for therapy. Prostate 71:649–658, 2011. © 2010 Wiley‐Liss, Inc.
Use of irinotecan for treatment of small cell carcinoma of the prostate
Authors: Tung Wei‐Lin , Wang Yuwei , Gout Peter W. , Liu Dean‐Mo , Gleave Martin , Wang Yuzhuo
Published: October 2010

BACKGROUND

Prostatic small cell carcinoma (SCC) is a rare variant of prostate cancer. It is extremely aggressive and resistant to available therapies with a median survival range of 5–17 months. No standard chemotherapeutic regimen has been established for its treatment. In search of a new therapeutic approach, we examined the response of patient‐derived prostatic SCC tissue xenografts to irinotecan, a topoisomerase I inhibitor.

METHODS

A tumor tissue line was established from a patient's prostatic SCC by subrenal capsule grafting using NOD‐SCID mice. Mice carrying subcutaneous transplants of the tumor line were then treated for 2 weeks with irinotecan alone and in combination with cisplatin. The effect on tumor volume, histopathology, and apoptosis were determined.

RESULTS

The prostatic SCC tissue line resembled the donor tissue in morphologic and immunohistochemical features. Irinotecan (20 mg/kg/day; days 1–3, 8–10) completely arrested xenograft growth with a small reduction in tumor volume and only minor weight loss of the hosts (7%); irinotecan (12 mg/kg; same schedule) + cisplatin (2.5 mg/kg/day; days 1 and 8) had a similar effect, but with lower weight loss. While the growth inhibition involved apoptosis, it was also associated with a marked increase in autophagy.

CONCLUSIONS

Tumor tissue lines established via subrenal capsule xenografting provide models with clinical relevance and the present study suggests that irinotecan could be useful for therapy of refractory prostatic SCC, in particular in combination with cisplatin. Prostate 71:675–681, 2011. © 2010 Wiley‐Liss, Inc.