bluuebunny/crossref_metadata_2025_split huggingface dataset:
2,3′,4,4′,5′‐Pentamethoxy‐trans‐stilbene, a resveratrol derivative, inhibits colitis‐associated colorectal carcinogenesis in mice
Authors: Li Haitao , Wu William Ka Kei , Li Zhi Jie , Chan Kam Ming , Wong Clover Ching Man , Ye Cai Guo , Yu Le , Sung Joseph Jao Yiu , Cho Chi Hin , Wang Mingfu 
Published: March 2010

Background and purpose:  Resveratrol, a naturally occurring polyphenolic antioxidant, has been shown to exhibit chemoprophylactic effects on cancer development. Previously, we reported that 2,3′,4,4′,5′‐pentamethoxy‐trans‐stilbene (PMS), a methoxylated resveratrol derivative, exerted a highly potent anti‐proliferative effect on human colon cancer cells as compared with its parent compound. In the present study, the chemopreventive effect of PMS was evaluated in a mouse model of colitis‐associated colon carcinogenesis.Experimental approach:  Seven‐week‐old Balb/c mice were injected i.p. with 10 mg·kg−1 azoxymethane (AOM). After 1 week, 3% dextran sodium sulphate (DSS) was administered in the drinking water for 7 days followed by 14 days of tap water for recovery, and this cycle was repeated twice.Key results:  Intragastric administration of PMS (25, 50 mg·kg−1 body weight) for 16 weeks significantly reduced the multiplicity of colonic neoplasms by 15% and 35% (P < 0.01) respectively. Moreover, PMS at 50 mg·kg−1 inhibited colon cancer cell proliferation and promoted apoptosis. Such changes were accompanied by reduction of Akt (protein kinase B) phosphorylation, inactivation of β‐catenin and down‐regulation of inducible nitric oxide synthase. In parallel, in vitro studies also demonstrated that PMS inhibited proliferation and induced apoptosis in the murine colon adenocarcinoma cell line Colon26 with concomitant inhibition of Akt phosphorylation and inactivation of β‐catenin.Conclusions and implications:  PMS effectively suppressed colon carcinogenesis in an AOM/DSS animal model and may merit further clinical investigation as a chemoprophylactic agent against colitis‐associated colon cancer in humans.
Quantification of brain endocannabinoid levels: methods, interpretations and pitfalls
Authors: Buczynski Matthew W , Parsons Loren H 
Published: March 2010

Endocannabinoids play an important role in a diverse range of neurophysiological processes including neural development, neuroimmune function, synaptic plasticity, pain, reward and affective state. This breadth of influence and evidence for altered endocannabinoid signalling in a variety of neuropathologies has fuelled interest in the accurate quantification of these lipids in brain tissue. Established methods for endocannabinoid quantification primarily employ solvent‐based lipid extraction with further sample purification by solid phase extraction. In recent years in vivo microdialysis methods have also been developed for endocannabinoid sampling from the brain interstitial space. However, considerable variability in estimates of endocannabinoid content has led to debate regarding the physiological range of concentrations present in various brain regions. This paper provides a critical review of factors that influence the quantification of brain endocannabinoid content as determined by lipid extraction from bulk tissue and by in vivo microdialysis. A variety of methodological issues are discussed including analytical approaches, endocannabinoid extraction and purification, post‐mortem changes in brain endocannabinoid content, cellular reactions to microdialysis probe implantation and caveats related to lipid sampling from the extracellular space. The application of these methods for estimating brain endocannabinoid content and the effects of endocannabinoid clearance inhibition are discussed. The benefits, limitations and pitfalls associated with each approach are emphasized, with an eye toward the appropriate interpretation of data gathered by each method.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Endocannabinoid signalling: has it got rhythm?
Authors: Vaughn Linda K , Denning Gerene , Stuhr Kara L , de Wit Harriet , Hill Matthew N , Hillard Cecilia J 
Published: March 2010

Endogenous cannabinoid signalling is widespread throughout the body, and considerable evidence supports its modulatory role in many fundamental physiological processes. The daily and seasonal cycles of the relationship of the earth and sun profoundly affect the terrestrial environment. Terrestrial species have adapted to these cycles in many ways, most well studied are circadian rhythms and hibernation. The purpose of this review was to examine literature support for three hypotheses: (i) endocannabinoid signalling exhibits brain region‐specific circadian rhythms; (ii) endocannabinoid signalling modulates the rhythm of circadian processes in mammals; and (iii) changes in endocannabinoid signalling contribute to the state of hibernation. The results of two novel studies are presented. First, we report the results of a study of healthy humans demonstrating that plasma concentrations of the endocannabinoid,N‐arachidonylethanolamine (anandamide), exhibit a circadian rhythm. Concentrations of anandamide are threefold higher at wakening than immediately before sleep, a relationship that is dysregulated by sleep deprivation. Second, we investigated differences in endocannabinoids and congeners in plasma fromMarmota monaxobtained in the summer and during the torpor state of hibernation. We report that 2‐arachidonoylglycerol is below detection inM. monaxplasma and that concentrations of anandamide are not different. However, plasma concentrations of the anorexigenic lipid oleoylethanolamide were significantly lower in hibernation, while the concentrations of palmitoylethanolamide and 2‐oleoylglycerol were significantly greater in hibernation. We conclude that available data support a bidirectional relationship between endocannabinoid signalling and circadian processes, and investigation of the contribution of endocannabinoid signalling to the dramatic physiological changes that occur during hibernation is warranted.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Nickel, cobalt and chromate sensitization and occupation*
Authors: Rui Francesca , Bovenzi Massimo , Prodi Andrea , Belloni Fortina Anna , Romano Ilaria , Peserico Andrea , Corradin Maria Teresa , Carrabba Enrico , Larese Filon Francesca 
Published: March 2010

Background: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis. Objectives: To estimate the prevalence of nickel, cobalt and chromate allergy in a population of consecutive patients and to investigate the possible association with individual and occupational risk factors. Patients/Methods: A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch tests. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. Results: About 24.6% of the patients reacted positively to nickel sulphate, 10.2% to cobalt chloride and 8.7% to potassium dichromate. Nickel sensitization was higher in women aged 26–35 years in comparison with the youngest group (15–25 years) and the older group (> 45 years). In women, the prevalence of positive reactions to nickel was positively associated with metal and mechanical work (OR 1.54; 95%, CI 1.16–2.05). Chromate sensitization was more prevalent in building trade workers for both women (OR 1.58; 95% CI 1.00–2.49) and men (OR 2.24; 95% CI 1.55–3.22). Cobalt sensitization was associated with textile and leather work in women (OR 1.52; 95% CI 1.09–2.12) and with cleaning work in men (OR 1.86; 95% CI 1.18–2.93). Conclusions: Our study showed interesting associations between some occupations and nickel, chromate and cobalt allergy.
Spectroscopic Imaging of Breast Cancer
Authors: Sijens P. E. , Dorrius M. D. 
Published: March 2010

SummarySingle voxel magnetic resonance spectroscopy (MRS) has been the standard in human breast tumour studies published to date. This method is hampered by the impossibility to study tissue heterogeneity or compare the metabolite signals in breast lesion directly to those in unaffected tissue. Multivoxel MRS studies, frequently referred to as spectroscopic imaging, while potentially allowing for truly quantitative tissue characterization, have up to now also been far from quantitative with, for example, the signal‐to‐noise ratio of the choline (Cho) signal serving as a measure of tumour activity. Demonstrated in this study is that in a standard clinical setting with a regular 1.5 T MR scanner, it is possible to perform quantitative multivoxel MRS. Using a pre‐measurement to map the distributions of water and fat, and literature values for the T1 and T2 relaxation times of Cho and water in fibroglandular breast tissue and tumours, one can determine the concentrations of Cho in different tumour compartments and surrounding tissues in two brief multivoxel MRS measurements. Quantitative diagnostic and follow‐up studies of focal breast pathology are now possible.
Breast Magnetic Resonance Imaging as a Problem‐Solving Modality?
Authors: Dorrius M. D. , Pijnappel R. M. , Oudkerk M. 
Published: March 2010

SummaryMammography is the primary imaging modality for the early detection of breast cancer. Because of the low predictive value of mammography, a large majority of patient referred for biopsy have benign disease. The question is whether magnetic resonance imaging (MRI) is a diagnostic alternative to biopsy for women with inconclusive findings at mammography or mammographic (Breast Imaging Reporting And Data System (BIRADS) 3 lesions. In this article the breast MRI and indications will be described. An overview will be given of MRI as a problem‐solving modality in mammographic BIRADS 3 lesions and inconclusive mammographic findings with and without microcalcifications. The negative predictive value of breast MRI must be sufficiently high to definitively indicate a lack of need for biopsy and thus to be an effective addition to the work‐up of mammographic BIRADS 3 lesions or inconclusive findings on mammography. Therefore, breast MRI should only be used for cases with proven diagnostic value.
Conventional Tc‐99m‐based Bone Scan Versus Fluoride Positron Emission Tomography Combined with Computed Tomography in the Assessment of Bone Metastases in Prostate Cancer Patients
Authors: Beheshti M. , Pirich C. , Langsteger W. 
Published: March 2010

SummaryIn prostate cancer, bone metastasis is related to a poor prognosis and is one of the major causes of morbidity and mortality. Detection of metastatic bone disease is particularly important in prostate cancer patients with high probability for distant metastases before embarking on radical prostatectomy or radiation therapy. The choice of imaging modalities that best depict the metastatic bony lesions may vary depending on different patterns of bone metastases. Bone scintigraphy has been used routinely in the evaluation of prostate cancer patients in the last decades. However, it suffers from adequate specificity. Single photon emission tomography (SPECT) increases the sensitivity and specificity of planar bone scanning especially for the evaluation of the spine. Recently, positron emission tomography (PET) using F‐18 Fluoride shows promising results in the detection of bone metastases especially in cancers with prominent osteoblasic pattern of bone metastases such as prostate cancer. This article reviews the value of conventional planar bone scanning, SPECT, SPECT/CT as well as F‐18 Fluoride PET/CT in the assessment of bone metastases in prostate cancer patients.
The Role of F‐18 Choline PET and PET/CT in Prostate Cancer
Authors: Kohlfürst S. , Malle P. , Igerc I. , Gallowitsch H. J. , Lind P. 
Published: March 2010

SummaryF‐18 fluorocholine [fluoromethyl‐dimethyl‐2‐hydroxyethyl‐ammonium (FCH)] is a choline analogue that shows great structural similarity to natural choline. The pathophysiological basis for the use of choline and its derivates for prostate cancer (PC) imaging are the elevation of choline levels and the up‐regulation of choline kinase activity in malignant cells. In order to allow rapid tumour growth, malignant cells are able to trap choline to produce phosphatidylcholine, part of the cellular membrane. As shown in recent studies, F‐18 choline PET and PET/CT might be a valuable tool in detecting the primary tumour in case of elevated prostate‐specific antigen (PSA) serum levels. However, data are not consistent, and further research is necessary before general recommendations concerning F‐18 choline PET and PET/CT can be given in this setting. Furthermore, some studies investigated the accuracy of F‐18 choline PET and PET/CT in detecting lymph node or bone metastases and local recurrences in case of PSA relapse in patients with a history of PC.
Proteomics Study of COI1‐regulated Proteins in Arabidopsis Flower
Authors: Chua Lingling , Shan Xiaoyi , Wang Junxia , Peng Wen , Zhang Guiyou , Xie Daoxin 
Published: March 2010

Abstract Jasmonates (JAs) are a new class of plant hormone that regulate expression of diverse genes to mediate various plant responses. The Arabidopsis F‐box protein COI1 is required for plant defense and male fertility in JA signal pathway. To further investigate the regulatory role of COI1 in male fertility, we compared the proteomics profiles of Arabidopsis wild type (WT) flowers with coi1‐1 mutant male‐sterile flowers using two‐dimensional difference gel electrophoresis coupled with matrix‐assisted laser desoption/ionization‐time‐of‐flight mass spectrometry. Sixteen proteins with potential function in specific biological processes such as metabolism processes and defense/stress responses were differentially expressed in WT and coi1‐1 mutant flowers. Verification on a phi class glutathione transferase AtGSTF9, one out of these 16 identified proteins, revealed that the expression of AtGSTF9 was severely downregulated in flowers of coi1‐1 mutant compared with that of WT. Further function analyses of these genes would provide new insights into the molecular basis of COI1‐regulated male fertility.
Differential gene and protein expression in primary gastric carcinomas and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis
Authors: XIE Hai Long , LI Zhi Yu , GAN Run Liang , LI Xiao Jie , ZHANG Qing Li , HUI Mei , ZHOU Xiu Tian 
Published: March 2010

OBJECTIVE:  To gain insight into the molecular events of lymph node metastasis of human gastric carcinoma.METHODS:  The gene expression profile of five matched primary gastric carcinomas and their lymph node metastases was analyzed by complementary DNA (cDNA) microarray. Differential genes were identified in the metastatic and corresponding primary tumor pairs. Among the differentially expressed genes, carbonic anhydrase II (CAII) and insulin‐like growth factor binding protein 4 (IGFBP 4) genes were detected by RT‐PCR. CTTN protein expression was examined by tissue microarray.RESULTS:  There was a high expression (over twofold) of 44 genes and a low expression (under twofold) of 32 genes in lymph node metastasis compared with primary gastric carcinoma, respectively. CAII mRNA was downregulated and IGFBP 4 mRNA was upregulated in paired lymph node metastases of gastric carcinomas. The overexpression of CTTN protein was related to the lymph node metastasis and the clinical stage of gastric carcinomas.CONCLUSION:  This study showed that there is a low expression of genes relative to growth signal and immune response in lymph node metastases, and a high expression of genes relative to growth factor, cell cycle, cell motility and adhesion in lymph node metastases compared with primary gastric carcinomas. The expression of CTTN was related to the invasion and metastasis of gastric cancer.
Evaluation for clinical utility of GPC3, measured by a commercially available ELISA kit with Glypican‐3 (GPC3) antibody, as a serological and histological marker for hepatocellular carcinoma
Authors: Yasuda Eisuke , Kumada Takashi , Toyoda Hidenori , Kaneoka Yuji , Maeda Atsuyuki , Okuda Seiji , Yoshimi Naoki , Kozawa Osamu 
Published: March 2010

Aims:  We evaluated the clinical utility of glypican‐3 (GPC3), which has been proposed as a potential novel tumor marker for hepatocellular carcinoma (HCC), as a serological and histological marker for HCC.Methods:  The serum GPC3 level was compared between 200 patients with HCC and 200 patients with chronic liver disease (CLD). In addition, the expression of GPC3 was examined with immunohistochemistry on 38 resected specimens from patients with HCC. A commercially available GPC3 antibody was used for these analyses.Results:  The median values of serum GPC3 in patients with HCC and with CLD were 924.8 pg/mL and 1161.6 pg/mL, respectively. We found no elevation of serum GPC3 level in patients with HCC in comparison with those with CLD; rather the level was higher in patients with CLD (P < 0.0001). In immunohistochemical analysis, 14 of 38 (36.9%) HCC tissues were positive for GPC3, whereas no corresponding non‐cancerous tissue was positive. The positivity for GPC3 tended to increase with pathologic decreased differentiation of HCC.Conclusions:  We did not find serum GPC3 level, measured by a commercially available ELISA kit with GPC3 antibody, to be useful in the diagnosis of HCC. However, we did observe increased GPC3 staining in HCC tissue with moderate or poor differentiation, suggesting that GPC3 is produced by HCC tumors. This lack of utility could have been due to the measuring procedure used in the present study. Further evaluation of GPC3 in HCC with other measuring procedures is needed.
Chymase inhibitor prevents the nonalcoholic steatohepatitis in hamsters fed a methionine‐ and choline‐deficient diet
Authors: Tashiro Keitaro , Takai Shinji , Jin Denan , Yamamoto Hiromi , Komeda Koji , Hayashi Michihiro , Tanaka Kazuhiko , Tanigawa Nobuhiko , Miyazaki Mizuo 
Published: March 2010

Aim: Mast cells may be involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). The mast cell protease chymase contributes to the formation of angiotensin II and matrix metalloproteinase (MMP)‐9, both of which are intimately involved in liver fibrosis. Therefore, we hypothesized that chymase plays an important role in the development of NASH.Methods: Hamsters were fed a methionine‐ and choline‐deficient (MCD) diet for 8 weeks. These animals were divided into two groups and received either TY‐51469 (1 mg/kg per day) or placebo. A third group was fed a normal diet as a control.Results: Total plasma bilirubin, triglycerides, and hyaluronic acid levels were significantly higher in the MCD diet‐fed hamsters than in the normal diet‐fed hamsters, but the levels were significantly lower in chymase inhibitor‐treated MCD diet‐fed hamsters than in placebo‐treated MCD diet‐fed hamsters. Using histological analysis, marked steatosis and fibrosis were observed in MCD diet‐fed hamsters, but these changes were significantly attenuated by treatment with the chymase inhibitor. Increases in mast cells and chymase‐positive cells were observed in the liver after the MCD diet, but the increases disappeared in the chymase inhibitor‐treated group. The significant increase observed in chymase activity in liver tissue extract from the MCD diet‐fed group was also reduced by treatment with the chymase inhibitor. Chymase inhibition significantly reduced not only angiotensin II expression but also matrix metallopeptidase 9 activity in MCD diet‐fed hamsters.Conclusion: These findings demonstrate that the mast cell protease chymase may play a crucial role in the development of NASH in hamsters.
Analysis of HLA‐DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA‐DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC
Authors: Nakamura Minoru , Yasunami Michio , Kondo Hisayoshi , Horie Hitomi , Aiba Yoshihiro , Komori Atsumasa , Migita Kiyoshi , Yatsuhashi Hiroshi , Ito Masahiro , Shimoda Shinji , Ishibashi Hiromi ,   PBC Study Group in NHOSLJ
Published: March 2010

Aims:  Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown.Methods:  We determined the HLA‐DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1–452‐month observation period.Results:  Anti‐gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20–850.1) and anti‐centromere antibodies (OR, 2.36, 95% CI, 1.28–4.35) were significant risk factors for jaundice‐ and nonjaundice‐type progression, respectively. HLA‐DRB1*0405 and *0803 predisposed patients to anti‐gp210 (OR, 1.61, 95% CI, 1.08–2.39) and anti‐centromere (OR, 2.30, 95% CI, 1.41–3.73) antibody production, respectively. HLA‐DRB1*1502 and *0901 patients were predisposed to nonjaundice‐type progression (OR, 1.98, 95% CI, 1.13–3.40 and OR, 1.78, 95% CI, 1.02–3.03), while HLA‐DRB1*0803 and *0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48–3.41 and OR, 1.53, 95% CI, 1.11–2.11, respectively). Stratifying patients by HLA‐DRB1 alleles revealed that anti‐gp210 antibodies was a strong risk factor, regardless of the HLA‐DRB1 alleles for jaundice‐type progression, while anti‐centromere antibodies was a significant risk factor for nonjaundice‐type progression in patients with HLA‐DRB1*0405 (OR, 6.89, 95% CI, 2.18–26.56) and ‐DRB1*0803 (OR, 5.42, 95% CI, 1.47–24.62) but not other HLA‐DRB1 alleles.Conclusions:  HLA‐DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.
The Connectivity Map Links Iron Regulatory Protein-1–Mediated Inhibition of Hypoxia-Inducible Factor-2a Translation to the Anti-inflammatory 15-deoxy-Δ12,14-Prostaglandin J2
Authors: Zimmer Michael , Lamb Justin , Ebert Benjamin L. , Lynch Mary , Neil Christopher , Schmidt Emmett , Golub Todd R. , Iliopoulos Othon 
Published: March 2010

Abstract
Hypoxia-inducible factors 1 and 2 (HIF1 and HIF2) are heterodimeric transcription factors consisting of α regulatory subunits and a constitutively expressed β subunit. The expression of α regulatory subunits is promoted by hypoxia, cancer-associated mutations, and inflammatory cytokines. Thus, HIF1 and HIF2 provide a molecular link between cancer and inflammation. We have recently identified novel small molecules that selectively inhibit translation of the HIF2a message and thereby powerfully inhibit the expression of HIF2a target genes. We report here that Connectivity Map analysis links three of these compounds to the anti-inflammatory cytokine 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2). As with our identified compounds, PGJ2 inhibits translation of the HIF2a message in a mammalian target of rapamycin–independent manner by promoting the binding of iron regulatory protein-1 (IRP1) to a noncanonical iron responsive element (IRE) embedded within the 5′-untranslated region of the HIF2a message. The IRE is necessary and sufficient for mediating the effect. Mutation of the IRE sequence, or downregulation of IRP1 expression, blocks the effect of PGJ2 on HIF2a translation. This is the first report of an endogenous natural molecule regulating HIF2a translation, and it suggests that part of the anti-inflammatory and putative antineoplastic effects of PGJ2 may be mediated through inhibition of HIF2a within tumor epithelial cells themselves and/or mesenchymal cells of the tumor microenvironment. Cancer Res; 70(8); 3071–9. ©2010 AACR.