bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease
Authors: Deshpande Vikram , Huck Amelia , Ooi Esther , Stone John H , Faquin William C , Nielsen G Petur 
Published: June 2012

Hashimoto thyroiditis (HT) and the fibrosing variant of Hashimoto thyroiditis (FVHT) are immune-mediated tumefactive lesions of the thyroid. Immunoglobulin G4-related disease (IgG4-RD) is now a widely recognised multi-organ system disease characterised by elevated serum and tissue concentrations of IgG4. In this study, the authors address several unresolved questions pertaining to the relationship between HT and FVHT, and the association of each of these diseases with IgG4-RD.The authors evaluated 28 consecutive cases of HT and nine cases of FVHT. The clinical, demographic and serological data were recorded. The slides were stained immunohistochemically using antibodies to IgG4 and IgG and the quantitative analysis was recorded. Data on thyroid function tests were available on seven cases of FVHT and 14 cases of HT. Based on the availability of data, hypothyroidism was noted in 62% (9/14) of HT and 86% of FVHT (6/7). FVHT demonstrated an exaggerated lobular pattern with lobules separated by cellular storiform-type fibrosis, resembling fibrosis seen in other forms of IgG-RD. The median IgG4 counts per high power field (×40) in HT and FVHT were 2.3 and 22, respectively. The median IgG4:IgG ratios in HT and FVHT were 0.11 and 0.58, respectively. The authors propose that FVHT belongs to the spectrum of IgG4-RD. Although a proportion of cases of HT show elevated numbers of IgG4 positive plasma cells, these cases lack the histological features typically associated with IgG4-RD, and thus the relationship between HT and IgG4-RD remains unproven.
Assessing user preferences for sexually transmitted infection testing services: a discrete choice experiment
Authors: Miners Alec , Llewellyn Carrie , Pollard Alex , Lagarde Mylene , Richardson Daniel , Cairns John , Fisher Martin , Smith Helen 
Published: June 2012

ObjectiveTo assess user preferences for different aspects of sexually transmitted infection (STI) testing services.DesignA discrete choice experiment.Setting14 centres offering tests for STIs in East Sussex, England.ParticipantsPeople testing for STIs.Main outcome measure(Adjusted) ORs in relation to preferred service characteristics.Results3358 questionnaires were returned; mean age 26 (SD 9.4) years. 70% (2366) were recruited from genitourinary medicine (GUM) clinics. The analysis suggested that the most important characteristics to users were whether ‘staff had specialist STI knowledge’ compared with ‘staff without it’ (OR 2.55; 95% CI 2.47 to 2.63) and whether ‘tests for all STIs’ were offered rather than ‘some’ (OR 2.19; 95% CI 2.12 to 2.25). They remained the most important two service characteristics despite stratifying the analysis by variables such as age and sex. Staff levels of expertise were viewed as particularly important by people attending CASH centres, women and non-men who have sex with men. A ‘text or call to a mobile phone’ and ‘dropping in and waiting’ were generally the preferred methods of results reporting and appointment system, respectively.ConclusionsThis study suggests that people testing for STIs place particular importance on testing for all infections rather than some and staff with specialist STI knowledge. Thus, targets based purely on waiting up to 48 h for an appointment are misguided from a user perspective.
Clinical value of blood glucose measurement in pet rabbits
Authors: Harcourt‐Brown F. M. , Harcourt‐Brown S.F. 
Published: June 2012

Blood glucose was measured with a portable glucose meter in 907 rabbits, including 238 clinically healthy ones. Blood glucose concentrations ranged from 1.2 to 30.1 mmol/l. Diabetes mellitus was not encountered. No significant effect of sex or sedation was found. Hypoglycaemia was seen in 16 rabbits including one with an insulinoma. There was a significant relationship between blood glucose, food intake, signs of stress and severity of clinical disease. Rabbits showing signs of stress had higher blood glucose than rabbits with no signs and rabbits that were totally anorexic had higher blood glucose values than those that were eating normally or those with reduced food intake. Severe hyperglycaemia (>20 mmol/l) was associated with conditions with a poor prognosis. Rabbits with confirmed intestinal obstruction had a mean blood glucose of 24.7 mmol/l (n = 18). This was significantly higher than the rabbits with confirmed gut stasis, which had a mean value of 8.5 mmol/l (n = 51). The conclusion of the study was that blood glucose is a measurable parameter that can be used to assess the severity of a rabbit's condition and help to differentiate between gut stasis and intestinal obstruction in rabbits that are anorexic.
Vav3-Rac1 Signaling Regulates Prostate Cancer Metastasis with Elevated Vav3 Expression Correlating with Prostate Cancer Progression and Posttreatment Recurrence
Authors: Lin Kai-Ti , Gong Jianli , Li Chien-Feng , Jang Te-Hsuan , Chen Wen-Ling , Chen Huei-Jane , Wang Lu-Hai 
Published: June 2012

Abstract
Prostate cancer remains the second leading cause of cancer death in men in the Western world. Yet current therapies do not significantly improve the long-term survival of patients with distant metastasis. In this study, we investigated the role of the guanine nucleotide exchange factor Vav3 in prostate cancer progression and metastasis and found that Vav3 expression correlated positively with prostate cancer cell migration and invasion. Stimulation of the receptor tyrosine kinase EphA2 by ephrinA1 resulted in recruitment and tyrosine phosphorylation of Vav3, leading to Rac1 activation as well as increased migration and invasion in vitro. Reduction of Vav3 resulted in fewer para-aortic lymph nodes and bone metastasis in vivo. Clinically, expression of Vav3 and EphA2 was elevated in late-stage and metastatic prostate cancers. Among patients with stage IIB or earlier prostate cancer, higher Vav3 expression correlated with lower cumulative biochemical failure-free survival, suggesting that Vav3 may represent a prognostic marker for posttreatment recurrence of prostate cancer. Together, our findings provide evidence that the Vav3-mediated signaling pathway may serve as a therapeutic target for prostate cancer metastasis. Cancer Res; 72(12); 3000–9. ©2012 AACR.
Dishonorable Discharge: The Oncogenic Roles of Cleaved E-Cadherin Fragments
Authors: David Justin M. , Rajasekaran Ayyappan K. 
Published: June 2012

Abstract
Strong cell–cell interactions represent a major barrier against cancer cell mobility, and loss of intercellular adhesion by E-cadherin is a fundamental change that occurs during the progression of cancer to invasive disease. However, some aggressive carcinomas retain characteristics of differentiated epithelial cells, including E-cadherin expression. Emerging evidence indicates that proteolysis of E-cadherin generates fragments that promote tumor growth, survival, and motility, suggesting that E-cadherin cleavage converts this tumor suppressor into an oncogenic factor. In this review we discuss the emerging roles of cleaved E-cadherin fragments as modulators of cancer progression, and explore the translational and clinical implications of this research. Cancer Res; 72(12); 2917–23. ©2012 AACR.
Targeting of a Conformationally Exposed, Tumor-Specific Epitope of EGFR as a Strategy for Cancer Therapy
Authors: Gan Hui K. , Burgess Antony W. , Clayton Andrew H. A. , Scott Andrew M. 
Published: June 2012

AbstractEpidermal growth factor receptor (EGFR) and its most common extracellular mutant, EGFRvIII, are important therapeutic targets in multiple cancer types. A number of monoclonal antibodies and small-molecule inhibitors against these receptors are now used for anticancer treatments. New insights into the structure and function of these receptors illustrate how they can be targeted in novel ways, with expected improvements in the therapeutic efficacy. Monoclonal antibody 806 (mAb806) is an antibody that targets a conformationally exposed epitope of wild-type EGFR when it is overexpressed on tumor cells or in the presence of oncogenic mutations such as EGFRvIII. The mechanism of action of mAb806, which allows for EGFR inhibition without normal tissue toxicity, creates opportunities for combination therapy and strongly suggests mAb806 will be a superior targeted delivery system for antitumor agents. Targeting of the epitope for mAb806 also appears to be an improved strategy to inhibit tumors that express EGFRvIII. This concept of conformational epitope targeting by antibodies reflects an underlying interplay between the structure and biology of different conformational forms of the EGFR family. Cancer Res; 72(12); 2924–30. ©2012 AACR.
The Oncogenic Lung Cancer Fusion Kinase CD74-ROS Activates a Novel Invasiveness Pathway through E-Syt1 Phosphorylation
Authors: Jun Hyun Jung , Johnson Hannah , Bronson Roderick T. , de Feraudy Sebastien , White Forest , Charest Alain 
Published: June 2012

Abstract
Patients with lung cancer often present with metastatic disease and therefore have a very poor prognosis. The recent discovery of several novel ROS receptor tyrosine kinase molecular alterations in non–small cell lung cancer (NSCLC) presents a therapeutic opportunity for the development of new targeted treatment strategies. Here, we report that the NSCLC-derived fusion CD74-ROS, which accounts for 30% of all ROS fusion kinases in NSCLC, is an active and oncogenic tyrosine kinase. We found that CD74-ROS–expressing cells were highly invasive in vitro and metastatic in vivo. Pharmacologic inhibition of CD74-ROS kinase activity reversed its transforming capacity by attenuating downstream signaling networks. Using quantitative phosphoproteomics, we uncovered a mechanism by which CD74-ROS activates a novel pathway driving cell invasion. Expression of CD74-ROS resulted in the phosphorylation of the extended synaptotagmin-like protein E-Syt1. Elimination of E-Syt1 expression drastically reduced invasiveness both in vitro and in vivo without modifying the oncogenic activity of CD74-ROS. Furthermore, expression of CD74-ROS in noninvasive NSCLC cell lines readily conferred invasive properties that paralleled the acquisition of E-Syt1 phosphorylation. Taken together, our findings indicate that E-Syt1 is a mediator of cancer cell invasion and molecularly define ROS fusion kinases as therapeutic targets in the treatment of NSCLC. Cancer Res; 72(15); 3764–74. ©2012 AACR.
Inhibitory Roles of Signal Transducer and Activator of Transcription 3 in Antitumor Immunity during Carcinogen-Induced Lung Tumorigenesis
Authors: Ihara Shoichi , Kida Hiroshi , Arase Hisashi , Tripathi Lokesh P. , Chen Yi-An , Kimura Tetsuya , Yoshida Mitsuhiro , Kashiwa Yozo , Hirata Haruhiko , Fukamizu Reiko , Inoue Ruriko , Hasegawa Kana , Goya Sho , Takahashi Ryo , Minami Toshiyuki , Tsujino Kazuyuki , Suzuki Mayumi , Kohmo Satoshi , Inoue Koji , Nagatomo Izumi , Takeda Yoshito , Kijima Takashi , Mizuguchi Kenji , Tachibana Isao , Kumanogoh Atsushi 
Published: June 2012

AbstractStat3 mediates a complex spectrum of cellular responses, including inflammation, cell proliferation, and apoptosis. Although evidence exists in support of a positive role for Stat3 in cancer, its role has remained somewhat controversial because of insufficient study of how its genetic deletion may affect carcinogenesis in various tissues. In this study, we show using epithelium-specific knockout mice (Stat3Δ/Δ) that Stat3 blunts rather than supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although Stat3Δ/Δ mice did not show any lung defects in terms of proliferation, apoptosis, or angiogenesis, they exhibited reduced urethane-induced tumorigenesis and increased antitumor inflammation and natural killer (NK) cell immunity. Comparative microarray analysis revealed an increase in Stat3Δ/Δ tumors in proinflammatory chemokine production and a decrease in MHC class I antigen expression associated with NK cell recognition. Consistent with these findings, human non–small cell lung cancer (NSCLC) cells in which Stat3 was silenced displayed an enhancement of proinflammatory chemokine production, reduced expression of MHC class I antigen, and increased susceptibility to NK cell–mediated cytotoxicity. In addition, supernatants from Stat3-silenced NSCLC cells promoted monocyte migration. Collectively, our findings argue that Stat3 exerts an inhibitory effect on antitumor NK cell immunity in the setting of carcinogen-induced tumorigenesis. Cancer Res; 72(12); 2990–9. ©2012 AACR.
Molecular Signature of Smoking in Human Lung Tissues
Authors: Bossé Yohan , Postma Dirkje S. , Sin Don D. , Lamontagne Maxime , Couture Christian , Gaudreault Nathalie , Joubert Philippe , Wong Vivien , Elliott Mark , van den Berge Maarten , Brandsma Corry A. , Tribouley Catherine , Malkov Vladislav , Tsou Jeffrey A. , Opiteck Gregory J. , Hogg James C. , Sandford Andrew J. , Timens Wim , Paré Peter D. , Laviolette Michel 
Published: June 2012

AbstractCigarette smoking is the leading risk factor for lung cancer. To identify genes deregulated by smoking and to distinguish gene expression changes that are reversible and persistent following smoking cessation, we carried out genome-wide gene expression profiling on nontumor lung tissue from 853 patients with lung cancer. Gene expression levels were compared between never and current smokers, and time-dependent changes in gene expression were studied in former smokers. A total of 3,223 transcripts were differentially expressed between smoking groups in the discovery set (n = 344, P &lt; 1.29 × 10−6). A substantial number of smoking-induced genes also were validated in two replication sets (n = 285 and 224), and a gene expression signature of 599 transcripts consistently segregated never from current smokers across all three sets. The expression of the majority of these genes reverted to never-smoker levels following smoking cessation, although the time course of normalization differed widely among transcripts. Moreover, some genes showed very slow or no reversibility in expression, including SERPIND1, which was found to be the most consistent gene permanently altered by smoking in the three sets. Our findings therefore indicate that smoking deregulates many genes, many of which reverse to normal following smoking cessation. However, a subset of genes remains altered even decades following smoking cessation and may account, at least in part, for the residual risk of lung cancer among former smokers. Cancer Res; 72(15); 3753–63. ©2012 AACR.
Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance
Authors: Zamboni William C. , Torchilin Vladimir , Patri Anil K. , Hrkach Jeff , Stern Stephen , Lee Robert , Nel Andre , Panaro Nicholas J. , Grodzinski Piotr 
Published: June 2012

AbstractHistorically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues, which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities that are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems that could not be effectively solved in the past and include overcoming formulation issues, multidrug-resistance phenomenon, and penetrating cellular barriers that may limit device accessibility to intended targets, such as the blood–brain barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise toward new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics. Clin Cancer Res; 18(12); 3229–41. ©2012 AACR.
Genetic Polymorphisms in MicroRNA-Related Genes as Predictors of Clinical Outcomes in Colorectal Adenocarcinoma Patients
Authors: Lin Moubin , Gu Jian , Eng Cathy , Ellis Lee M. , Hildebrandt Michelle A. , Lin Jie , Huang Maosheng , Calin George A. , Wang Dingzhi , DuBois Raymond N. , Hawk Ernest T. , Wu Xifeng 
Published: June 2012

Abstract
Purpose: To evaluate the effects of single-nucleotide polymorphisms (SNP) in microRNA-related genes on clinical outcomes in patients with colorectal cancer (CRC) receiving first-line fluoropyrimidine-based chemotherapy.
Experimental Design: Forty-one SNPs in 26 microRNA-related genes were genotyped in 1,097 patients with CRC recruited at the University of Texas MD Anderson Cancer Center (Houston, TX). Patients were enrolled between 1990 and 2008 and last follow-up was in 2010. The associations between genotypes and recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) stratified by clinical stage were analyzed in 741 newly diagnosed patients (diagnosed within 1 year) and replicated the findings in an additional 356 patients.
Results: In patients with stage III disease, mir608: rs4919510 was associated with increased risk for both recurrence [HR, 2.72; 95% confidence interval (CI), 1.38–5.33] and death (HR, 3.53; 95%CI, 1.42–8.73). The associations were confirmed in the replication set, and the combined HRs for training and replication sets were 1.65 (95% CI, 1.13–2.41) for recurrence and 1.96 (95% CI, 1.19–3.21) for death, respectively. The mir219-1:rs213210 showed consistent association with death in the training set (HR, 3.86; 95% CI, 1.33–11.22), the replication set (HR, 3.33; 95% CI, 1.39–7.98), and combined data set (HR, 3.22; 95% CI, 1.70–6.10). In combined analysis of these two SNPs, patients carrying the variant genotypes at both sites exhibited a 5.6-fold increased risk of death.
Conclusion: Genetic polymorphisms in the microRNA pathway may predict prognosis in patients with stage III CRC treated with fluoropyrimidine-based chemotherapy. Clin Cancer Res; 18(14); 3982–91. ©2012 AACR.
Analysis of Receptor Tyrosine Kinase ROS1-Positive Tumors in Non–Small Cell Lung Cancer: Identification of a FIG-ROS1 Fusion
Authors: Rimkunas Victoria M. , Crosby Katherine E. , Li Daiqiang , Hu Yerong , Kelly Meghan E. , Gu Ting-Lei , Mack Jennifer S. , Silver Matthew R. , Zhou Xinmin , Haack Herbert 
Published: June 2012

Abstract
Purpose: To deepen our understanding of mutant ROS1 expression, localization, and frequency in non–small cell lung cancer (NSCLC), we developed a highly specific and sensitive immunohistochemistry (IHC)-based assay that is useful for the detection of wild-type and mutant ROS1.
Experimental Design: We analyzed 556 tumors with the ROS1 D4D6 rabbit monoclonal antibody IHC assay to assess ROS1 expression levels and localization. A subset of tumors was analyzed by FISH to determine the percentage of these tumors harboring ROS1 translocations. Using specific and sensitive IHC assays, we analyzed the expression of anaplastic lymphoma kinase (ALK), EGFR L858R, and EGFR E746-A750del mutations in a subset of lung tumors, including those expressing ROS1.
Results: In our NSCLC cohort of Chinese patients, we identified 9 (1.6%) tumors expressing ROS1 and 22 (4.0%) tumors expressing ALK. FISH identified tumors with ALK or ROS1 rearrangements, and IHC alone was capable of detecting all cases with ALK and ROS1 rearrangements. ROS1 fusion partners were determined by reverse transcriptase PCR identifying CD74-ROS1, SLC34A2-ROS1, and FIG-ROS1 fusions. Some of the ALK and ROS1 rearranged tumors may also harbor coexisting EGFR mutations.
Conclusions: NSCLC tumors with ROS1 rearrangements are uncommon in the Chinese population and represent a distinct entity of carcinomas. The ROS1 IHC assay described here is a valuable tool for identifying patients expressing mutant ROS1 and could be routinely applied in clinical practice to detect lung cancers that may be responsive to targeted therapies. Clin Cancer Res; 18(16); 4449–57. ©2012 AACR.
Emerging Roles of Angiopoietin-like 4 in Human Cancer
Authors: Tan Ming Jie , Teo Ziqiang , Sng Ming Keat , Zhu Pengcheng , Tan Nguan Soon 
Published: June 2012

Abstract
Angiopoietin-like 4 (ANGPTL4) is best known for its role as an adipokine involved in the regulation of lipid and glucose metabolism. The characterization of ANGPTL4 as an adipokine is largely due to our limited understanding of the interaction partners of ANGPTL4 and how ANGPTL4 initiates intracellular signaling. Recent findings have revealed a critical role for ANGPTL4 in cancer growth and progression, anoikis resistance, altered redox regulation, angiogenesis, and metastasis. Emerging evidence suggests that ANGPTL4 function may be drastically altered depending on the proteolytic processing and posttranslational modifications of ANGPTL4, which may clarify several conflicting roles of ANGPTL4 in different cancers. Although the N-terminal coiled-coil region of ANGPTL4 has been largely responsible for the endocrine regulatory role in lipid metabolism, insulin sensitivity, and glucose homeostasis, it has now emerged that the COOH-terminal fibrinogen-like domain of ANGPTL4 may be a key regulator in the multifaceted signaling during cancer development. New insights into the mechanistic action of this functional domain have opened a new chapter into the possible clinical application of ANGPTL4 as a promising candidate for clinical intervention in the fight against cancer. This review summarizes our current understanding of ANGPTL4 in cancer and highlights areas that warrant further investigation. A better understanding of the underlying cellular and molecular mechanisms of ANGPTL4 will reveal novel insights into other aspects of tumorigenesis and the potential therapeutic value of ANGPTL4. Mol Cancer Res; 10(6); 677–88. ©2012 AACR.
Resveratrol Helps Recovery from Fatty Liver and Protects against Hepatocellular Carcinoma Induced by Hepatitis B Virus X Protein in a Mouse Model
Authors: Lin Hsiu-Ching , Chen Yi-Fan , Hsu Wen-Hsin , Yang Chu-Wen , Kao Cheng-Heng , Tsai Ting-Fen 
Published: June 2012

Abstract
Resveratrol is a natural polyphenol that has beneficial effects across species and various disease models. Here, we investigate whether resveratrol is effective against hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) using HBV X protein (HBx) transgenic mice. We found that resveratrol (30 mg/kg/d) has a therapeutic effect on HBx-induced fatty liver and the early stages of liver damage. Resveratrol decreased intracellular reactive oxygen species and transiently stimulated hepatocyte proliferation. Interestingly, resveratrol inhibited LXRα and downregulated the expression of the lipogenic genes, Srebp1-c and PPARγ. The decrease in Srebp1-c seems to further downregulate the expression of its target genes, Acc and Fas. In addition, resveratrol stimulated the activity of Ampk and SirT1. Thus, resveratrol has a pleiotropic effect on HBx transgenic mice in terms of the downregulation of lipogenesis, the promotion of transient liver regeneration, and the stimulation of antioxidant activity. Furthermore, at the later precancerous stages, resveratrol delayed HBx-mediated hepatocarcinogenesis and reduced HCC incidence from 80% to 15%, a 5.3-fold reduction. Resveratrol should be considered as a potential chemopreventive agent for HBV-associated HCC. Cancer Prev Res; 5(7); 952–62. ©2012 AACR.