bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Quantum Dots‐Based Biotechnology in Cancer Diagnosis: Current Status and Future Perspectives
Authors: Peng Chun-Wei , Li Yan
Published: March 2010

The semiconductor nanocrystal quantum dots (QDs) have excellent photo‐physical properties, and the QDs‐based probes have achieved encouraging developments in cellular and in vivo molecular imaging. More and more researches showed that QDs‐based technology may become a promising approach in cancer research. In this review, we focus on recent application of QDs in cancer diagnosis and treatment, including early detection of primary tumor such as ovarian cancer, breast cancer, prostate cancer and pancreatic cancer, as well as regional lymph nodes and distant metastases. With the development of QDs synthesis and modification, the effect of QDs on tumor metastasis investigation will become more and more important in the future.
CORDIC Architectures: A Survey
Authors: Lakshmi B. , Dhar A. S.
Published: March 2010

In the last decade, CORDIC algorithm has drawn wide attention from academia and industry
for various applications such as DSP, biomedical signal processing, software defined radio, neural
networks, and MIMO systems to mention just a few. It is an iterative algorithm, requiring simple
shift and addition operations, for hardware realization of basic elementary functions. Since
CORDIC is used as a building block in various single chip solutions, the critical aspects to be
considered are high speed, low power, and low area, for achieving reasonable overall performance.
In this paper, we first classify the CORDIC algorithm based on the number system and discuss
its importance in the implementation of CORDIC algorithm. Then, we present systematic and
comprehensive taxonomy of rotational CORDIC algorithms, which are subsequently discussed
in depth. Special attention has been devoted to the higher radix and flat techniques proposed
in the literature for reducing the latency. Finally, detailed comparison of various algorithms is
presented, which can provide a first-order information to designers looking for either further
improvement of performance or selection of rotational CORDIC for a specific application.
A Theoretical Development of Distance Measure for Intuitionistic Fuzzy Numbers
Authors: Guha Debashree , Chakraborty Debjani
Published: March 2010

The objective of this paper is to introduce a distance measure for intuitionistic fuzzy numbers. Firstly the existing distance measures for intuitionistic fuzzy sets are analyzed and compared with the help of some examples. Then the new distance measure for intuitionistic fuzzy numbers is proposed based on interval difference. Also in particular the type of distance measure for triangle intuitionistic fuzzy numbers is described. The metric properties of the proposed measure are also studied. Some numerical examples are considered for applying the proposed measure and finally the result is compared with the existing ones.
Comparative Evaluation of Single‐Channel MMSE‐Based Noise Reduction Schemes for Speech Recognition
Authors: Principi Emanuele , Cifani Simone , Rotili Rudy , Squartini Stefano , Piazza Francesco
Published: March 2010

One of the big challenges in the field of Automatic
Speech Recognition (ASR) consists in developing suitable solutions
able to work properly also in adverse acoustic conditions,
like in presence of additive noise and/or in reverberant rooms.
Recently a certain attention has been paid to deeply integrate the
noise suppressor in the feature extraction pipeline. In this paper,
different single‐channel MMSE‐based noise reduction schemes
have been implemented both in the frequency and cepstral
domains and the related recognition performances evaluated on
the AURORA2 and AURORA4 databases, therefore providing a
useful reference for the scientific community.
Effect of Honey and Eugenol on Ehrlich Ascites and Solid Carcinoma
Authors: Jaganathan Saravana Kumar , Mondhe Dilip , Wani Z. A. , Pal Harish C. , Mandal Mahitosh
Published: March 2010

Ehrlich ascites carcinoma is a spontaneous murine mammary adenocarcinoma adapted to ascites form and carried in outbred mice by serial intraperitoneal (i/p) passages. The previous work from our laboratory showed that honey having higher phenolic content was potent in inhibiting colon cancer cell proliferation. In this work, we extended our research to screen the antitumor activity of two selected honey samples and eugenol (one of the phenolic constituents of honey) against murine Ehrlich ascites and solid carcinoma models. Honey containing higher phenolic content was found to significantly inhibit the growth of Ehrlich ascites carcinoma as compared to other samples. When honey containing higher phenolic content was given at 25% (volume/volume) intraperitoneally (i/p), the maximum tumor growth inhibition was found to be 39.98%. However, honey was found to be less potent in inhibiting the growth of Ehrlich solid carcinoma. On the other hand, eugenol at a dose of 100 mg/kg i/p was able to inhibit the growth of Ehrlich ascites by 28.88%. In case of solid carcinoma, eugenol (100 mg/kg; i/p) showed 24.35% tumor growth inhibition. This work will promote the development of honey and eugenol as promising candidates in cancer chemoprevention.
Genetic Screen Identifies Insulin-like Growth Factor Binding Protein 5 as a Modulator of Tamoxifen Resistance in Breast Cancer
Authors: Ahn Bo Young , Elwi Adam N. , Lee Byoungchun , Trinh Diane L.N. , Klimowicz Alexander C. , Yau Annie , Chan Jennifer A. , Magliocco Anthony , Kim Sung-Woo
Published: March 2010

Tamoxifen resistance is one of the overarching challenges in the treatment of patients with estrogen receptor (ER)–positive breast cancer. Through a genome-wide RNA interference screen to discover genes responsible for tamoxifen resistance in vitro, we identified insulin-like growth factor binding protein 5 (IGFBP5) as a determinant of drug sensitivity. Specific knockdown of IGFBP5 by retroviral infection with short hairpin RNA–expressing cassette in MCF7 human breast cancer cells (pRS-shIGFBP5) conferred tamoxifen resistance in vitro due to concomitant loss of ERα expression and signaling. IGFBP5 expression was also reduced in MCF7 cells selected for tamoxifen resistance in culture (TAMR). Both tamoxifen-resistant MCF7-TAMR and MCF7-pRS-shIGFBP5 cells could be resensitized to drug by treatment with exogenous recombinant IGFBP5 (rIGFBP5) protein. Treatment with rIGFBP5 protein in mouse tumor xenografts reversed the in vivo tamoxifen resistance of MCF7-pRS-shIGFBP5 cell–derived tumors by reducing tumor cell proliferation. IGFBP5 immunohistochemical staining in a cohort of 153 breast cancer patients showed that low IGFBP5 expression was associated with shorter overall survival after tamoxifen therapy. Thus, IGFBP5 warrants investigation as an agent to reverse tamoxifen resistance. Cancer Res; 70(8); 3013–9. ©2010 AACR.
Noscapine, a Benzylisoquinoline Alkaloid, Sensitizes Leukemic Cells to Chemotherapeutic Agents and Cytokines by Modulating the NF-κB Signaling Pathway
Authors: Sung Bokyung , Ahn Kwang Seok , Aggarwal Bharat B.
Published: March 2010

Noscapine, a benzylisoquinoline alkaloid derived from opium, was recently reported to exhibit activity against a variety of cancers through a poorly understood mechanism. Because the transcription factor NF-κB has been linked with inflammation, survival, proliferation, invasion, and angiogenesis in tumors, we hypothesized that noscapine mediates its effects by modulating the NF-κB activation pathway. We found that noscapine potentiates apoptosis induced by cytokines and chemotherapeutic agents in tumor cells. Noscapine alone suppressed proliferation of human leukemia and myeloma cells and downregulated the constitutive expression of cell survival proteins. Noscapine also abrogated the inducible expression of proteins involved in survival, proliferation, invasion, and angiogenesis, all of which are regulated by NF-κB. Noscapine suppressed both inducible and constitutive NF-κB activation in tumor cells through inhibition of IκB kinase, leading to inhibition of phosphorylation and degradation of IκBα. Noscapine also suppressed phosphorylation and nuclear translocation of p65, leading to inhibition of NF-κB reporter activity induced by various components of the NF-κB activation pathway. Activity of the NF-κB–containing cyclooxygenase-2 promoter was also inhibited by noscapine. Thus, noscapine inhibits the proliferation of leukemia cells and sensitizes them to tumor necrosis factor and chemotherapeutic agents by suppressing the NF-κB signaling pathway. Cancer Res; 70(8); 3259–68. ©2010 AACR.
β-Ionone Enhances TRAIL-Induced Apoptosis in Hepatocellular Carcinoma Cells through Sp1-Dependent Upregulation of DR5 and Downregulation of NF-κB Activity
Authors: Kim Mun-Ock , Moon Dong-Oh , Kang Chang-Hee , Kwon Taeg Kyu , Choi Yung Hyun , Kim Gi-Young
Published: March 2010

β-Ionone (ION), an end-ring analogue of β-carotenoid, has been known to inhibit tumor cell growth and induce apoptosis in various types of cancer cells. Nevertheless, its apoptosis-related molecular mechanisms remain unclear. Here, we first investigated the molecular mechanisms by which ION sensitizes cancer cells to the therapeutic potential of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Notably, treatment with subtoxic concentrations of ION and TRAIL effectively inhibited cell viability in the hepatocellular carcinoma cell line Hep3B and other cancer cell lines such as colon carcinoma cell line HCT116 and leukemia cell line U937. Combined treatment with ION and TRAIL was also more effective in inducing DR5 expression, caspase activities, and apoptosis than treatment with either agent alone. ION-mediated sensitization to TRAIL was efficiently reduced by treatment with a chimeric blocking antibody or small interfering RNA specific for DR5. Electrophoretic mobility shift assay and a chromatin immunoprecipitation assay confirmed that ION treatment upregulates the binding of transcription factor Sp1 to its putative site within the DR5 promoter region, suggesting that Sp1 is an ION-responsive transcription factor. In addition, ION significantly increased hepatocellular carcinoma cell sensitivity to TRAIL by abrogating TRAIL-induced NF-κB activation and decreasing the expression of antiapoptotic proteins such as XIAP and IAP-1/2. Taken together, these data suggest that ION is a useful agent for TRAIL-based cancer treatments. Mol Cancer Ther; 9(4); 833–43. ©2010 AACR.
Subcellular Distribution of a Fluorescence-Labeled Combi-Molecule Designed to Block Epidermal Growth Factor Receptor Tyrosine Kinase and Damage DNA with a Green Fluorescent Species
Authors: Todorova Margarita I. , Larroque Anne-Laure , Dauphin-Pierre Sabine , Fang You-Qiang , Jean-Claude Bertrand J.
Published: March 2010

To monitor the subcellular distribution of mixed epidermal growth factor (EGF) receptor (EGFR)–DNA targeting drugs termed combi-molecules, we designed AL237, a fluorescent prototype, to degrade into a green fluorescent DNA damaging species and FD105, a blue fluorescent EGFR inhibitor. Here we showed that AL237 damaged DNA in the 12.5 to 50 μmol/L range. Despite its size, it blocked EGFR phosphorylation in an enzyme assay (IC50 = 0.27 μmol/L) and in MDA-MB468 breast cancer cells in the same concentration range as for DNA damage. This translated into inhibition of extracellular signal-regulated kinase 1/2 or BAD phosphorylation and downregulation of DNA repair proteins (XRCC1, ERCC1). Having shown that AL237 was a balanced EGFR-DNA targeting molecule, it was used as an imaging probe to show that (a) green and blue colors were primarily colocalized in the perinuclear and partially in the nucleus in EGFR- or ErbB2-expressing cells, (b) the blue fluorescence associated with FD105, but not the green, was colocalized with anti-EGFR red-labeled antibody, (c) the green fluorescence of nuclei was significantly more intense in NIH 3T3 cells expressing EGFR or ErbB2 than in their wild-type counterparts (P < 0.05). Similarly, the growth inhibitory potency of AL237 was selectively stronger in the transfectants. In summary, the results suggest that AL237 diffuses into the cells and localizes abundantly in the perinuclear region and partially in the nucleus where it degrades into EGFR and DNA targeting species. This bystander-like effect translates into high levels of DNA damage in the nucleus. Sufficient quinazoline levels are released in the cells to block EGF-induced activation of downstream signaling. Mol Cancer Ther; 9(4); 869–82. ©2010 AACR.
Inhibition of Aldose Reductase Prevents Growth Factor–Induced G1-S Phase Transition through the AKT/Phosphoinositide 3-Kinase/E2F-1 Pathway in Human Colon Cancer Cells
Authors: Ramana Kota V. , Tammali Ravinder , Srivastava Satish K.
Published: March 2010

Colon cancer is the leading cause of cancer death in both men and women worldwide. The deregulated cell cycle control or decreased apoptosis of normal epithelial cells leading to uncontrolled proliferation is one of the major features of tumor progression. We have previously shown that aldose reductase (AR), a NADPH-dependent aldo-keto reductase, has been shown to be involved in growth factor–induced proliferation of colon cancer cells. Herein, we report that inhibition of AR prevents epidermal growth factor (EGF)– and basic fibroblast growth factor (bFGF)–induced HT29 cell proliferation by accumulating cells at G1 phase of cell cycle. Similar results were observed in SW480 and HCT-116 colon cancer cells. Treatment of HT29 cells with AR inhibitor, sorbinil or zopolrestat, prevented the EGF- and bFGF-induced DNA binding activity of E2F-1 and phosphorylation of retinoblastoma protein. Inhibition of AR also prevented EGF- and bFGF-induced phosphorylation of cyclin-dependent kinase (cdk)-2 and expression of G1-S transition regulatory proteins such as cyclin D1, cdk4, proliferating cell nuclear antigen, cyclin E, and c-myc. More importantly, inhibition of AR prevented the EGF- and bFGF-induced activation of phosphoinositide 3-kinase/AKT and reactive oxygen species generation in colon cancer cells. Further, inhibition of AR also prevented the tumor growth of human colon cancer cells in nude mouse xenografts. Collectively, these results show that AR mediates EGF- and bFGF-induced colon cancer cell proliferation by activating or expressing G1-S phase proteins such as E2F-1, cdks, and cyclins through the reactive oxygen species/phosphoinositide 3-kinase/AKT pathway, indicating the use of AR inhibitors in the prevention of colon carcinogenesis. Mol Cancer Ther; 9(4); 813–24. ©2010 AACR.
Phospholipase A2 Activity of Peroxiredoxin 6 Promotes Invasion and Metastasis of Lung Cancer Cells
Authors: Ho Jin-Nyoung , Lee Seung Bum , Lee Seung-Sook , Yoon Sung Hwan , Kang Ga Young , Hwang Sang-Gu , Um Hong-Duck
Published: March 2010

Peroxiredoxins (PRDX) are a family of thiol-dependent peroxidases. Among the six mammalian members of this family, PRDX6 is the only protein that additionally exhibits phospholipase A2 (PLA2) activity. The physiologic role of this interesting PRDX6 feature is largely unknown at present. In this study, we show that PRDX6 increases the metastatic potential of lung cancer cells. Functional analyses of the enzymatic activities of PRDX6, using specific pharmacologic inhibitors and mutagenesis studies, reveal that both peroxidase and PLA2 activities are required for metastasis. Specifically, peroxidase activity facilitates the growth of cancer cells, and PLA2 activity promotes invasiveness. Further investigation of the latter event discloses that PLA2 activity promotes accumulation of arachidonic acid, which, in turn, induces the invasive pathway involving p38 kinase, phosphoinositide 3-kinase, Akt, and urokinase-type plasminogen activator. This study is the first to define the functions of the enzymatic activities of PRDX6 in metastasis and to show the involvement of arachidonic acid in PRDX6 action in intact cells. These novel findings provide a significant step toward elucidating the role of PRDX6 in cancer and the mechanism of its action. Mol Cancer Ther; 9(4); 825–32. ©2010 AACR.
Erythropoietin-Induced Activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK Pathways Promotes Malignant Cell Behavior in a Modified Breast Cancer Cell Line
Authors: Shi Zhanzhong , Hodges Vivien M. , Dunlop Elaine A. , Percy Melanie J. , Maxwell Alexander P. , El-Tanani Mohamed , Lappin Terry R.J.
Published: March 2010

Erythropoietin (Epo), the major regulator of erythropoiesis, and its cognate receptor (EpoR) are also expressed in nonerythroid tissues, including tumors. Clinical studies have highlighted the potential adverse effects of erythropoiesis-stimulating agents when used to treat cancer-related anemia. We assessed the ability of EpoR to enhance tumor growth and invasiveness following Epo stimulation. A benign noninvasive rat mammary cell line, Rama 37, was used as a model system. Cell signaling and malignant cell behavior were compared between parental Rama 37 cells, which express few or no endogenous EpoRs, and a modified cell line stably transfected with human EpoR (Rama 37-28). The incubation of Rama 37-28 cells with pharmacologic levels of Epo led to the rapid and sustained increases in phosphorylation of signal transducers and activators of transcription 5, Akt, and extracellular signal-regulated kinase. The activation of these signaling pathways significantly increased invasion, migration, adhesion, and colony formation. The Epo-induced invasion capacity of Rama 37-28 cells was reduced by the small interfering RNA–mediated knockdown of EpoR mRNA levels and by inhibitors of the phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase signaling pathways with adhesion also reduced by Janus-activated kinase 2/signal transducers and activators of transcription 5 inhibition. These data show that Epo induces phenotypic changes in the behavior of breast cancer cell lines and establishes links between individual cell signaling pathways and the potential for cancer spread. Mol Cancer Res; 8(4); 615–26. ©2010 AACR.
Prostaglandin E2 Promotes Lung Cancer Cell Migration via EP4-βArrestin1-c-Src Signalsome
Authors: Kim Jae Il , Lakshmikanthan Vijayabaskar , Frilot Nicole , Daaka Yehia
Published: March 2010

Many human cancers express elevated levels of cyclooxygenase-2 (COX-2), an enzyme responsible for the biosynthesis of prostaglandins. Available clinical data establish the protective effect of COX-2 inhibition on human cancer progression. However, despite these encouraging outcomes, the appearance of unwanted side effects remains a major hurdle for the general application of COX-2 inhibitors as effective cancer drugs. Hence, a better understanding of the molecular signals downstream of COX-2 is needed for the elucidation of drug targets that may improve cancer therapy. Here, we show that the COX-2 product prostaglandin E2 (PGE2) acts on cognate receptor EP4 to promote the migration of A549 lung cancer cells. Treatment with PGE2 enhances tyrosine kinase c-Src activation, and blockade of c-Src activity represses the PGE2-mediated lung cancer cell migration. PGE2 affects target cells by activating four receptors named EP1 to EP4. Use of EP subtype-selective ligand agonists suggested that EP4 mediates prostaglandin-induced A549 lung cancer cell migration, and this conclusion was confirmed using a short hairpin RNA approach to specifically knock down EP4 expression. Proximal EP4 effectors include heterotrimeric Gs and βArrestin proteins. Knockdown of βArrestin1 expression with shRNA significantly impaired the PGE2-induced c-Src activation and cell migration. Together, these results support the idea that increased expression of the COX-2 product PGE2 in the lung tumor microenvironment may initiate a mitogenic signaling cascade composed of EP4, βArrestin1, and c-Src which mediates cancer cell migration. Selective targeting of EP4 with a ligand antagonist may provide an efficient approach to better manage patients with advanced lung cancer. Mol Cancer Res; 8(4); 569–77. ©2010 AACR.
Energy Balance, the PI3K-AKT-mTOR Pathway Genes, and the Risk of Bladder Cancer
Authors: Lin Jie , Wang Jianming , Greisinger Anthony J. , Grossman H. Barton , Forman Michele R. , Dinney Colin P. , Hawk Ernest T. , Wu Xifeng
Published: March 2010

We evaluated the association between energy balance and risk of bladder cancer and assessed the joint effects of genetic variants in the mammalian target of rapamycin (mTOR) pathway genes with energy balance. The study included 803 Caucasian bladder cancer patients and 803 healthy Caucasian controls matched to cases by age (±5 years) and gender. High energy intake [odds ratio, 1.60; 95% confidence interval (95% CI), 1.23-2.09] and low physical activity (odds ratio, 2.82; 95% CI, 2.10-3.79) were each associated with significantly increased risk of bladder cancer with dose-response pattern (Ptrend < 0.001). However, obesity (body mass index, ≥30) was not associated with the risk. Among 222 single nucleotide polymorphisms, 28 single nucleotide polymorphisms located in six genes of mTOR pathway were significantly associated with the risk. Further, the risk associated with high energy intake and low physical activity was only observed among subjects carrying a high number of unfavorable genotypes in the pathway. Moreover, when physical activity, energy intake, and genetic variants were analyzed jointly, the study population was clearly stratified into a range of low- to high-risk subgroups as defined energy balance status. Compared with subjects within the most favorable energy balance category (low energy intake, intensive physical activity, low number of unfavorable genotypes), subjects in the worst energy balance category (high energy intake, low physical activity, and carrying ≥7 unfavorable genotypes) had 21.93-fold increased risk (95% CI, 6.7-71.77). Our results provide the first strong evidence that physical activity, energy intake, and genetic variants in the mTOR pathway jointly influence bladder cancer susceptibility and that these results have implications for bladder cancer prevention. Cancer Prev Res; 3(4); 505–17. ©2010 AACR.
NF-κB Fans the Flames of Lung Carcinogenesis
Authors: Wong Kwok-Kin , Jacks Tyler , Dranoff Glenn
Published: March 2010

This perspective on Deng et al. (beginning on p. 424 in this issue of the journal) examines the link between NF-κB and lung tumorigenesis. Experiments in genetically engineered mouse models of lung cancers are elucidating protumorigenic roles of NF-κB activation in lung cancer pathogenesis. Our growing understanding of the tumor-promoting NF-κB downstream effector pathways could lead to the development of novel approaches for lung cancer therapy and chemoprevention. Cancer Prev Res; 3(4); 403–5. ©2010 AACR.
Unprecedented Opportunities and Promise for Cancer Prevention Research
Authors: Blackburn Elizabeth H. , Tlsty Thea D. , Lippman Scott M.
Published: March 2010

Cancer prevention encompasses a wide range of highly developed science and clinical impact. Enunciating these two aspects in the same breath highlights the crucial link between them. The breadth and excitement of current opportunities in the science of cancer prevention have never been greater. Major avenues of such research include the extent and effect of premalignancy, the molecular underpinnings of carcinogenesis and related prevention targets, in vitro model systems of the progression of normal human epithelial cells to tumorigenesis, molecular risk stratification and pharmacogenomic approaches, and many more. We describe the clinical impacts of cancer prevention (with examples in the areas of molecular targeting, vaccines, epidemiology, and behavioral science) and the stage-setting science that facilitated them. In addition, discussed are new prevention opportunities such as interactions between stromal and microenvironmental factors, the control of premalignant stem cell phenotypes through epigenetic reprogramming, and neoplastic cells and various stress responses including those involving telomere biology. The promise of this science, particularly integrative, interdisciplinary research, is to hasten the ability of clinical prevention to reduce the burden of cancer. Cancer Prev Res; 3(4); 394–402. ©2010 AACR.
Mucinous Cystadenomas in Liver: Management and Origin
Authors: Erdogan D. , Kloek J. , Lamers W.H. , Offerhaus G.J.A. , Busch O.R.C. , Gouma D.J. , van Gulik T.M.
Published: March 2010

Background: Mucinous cystadenomas of the liver are rare cystic neoplasms. The aim of this study was to assess management of a consecutive series of patients who underwent laparotomy for a suspected cystadenoma or cystadenocarcinoma. Secondly, the origin of ovarian stroma (OS) in mucinous liver cystadenomas was examined during early embryonic development. Patients and Methods: Patients diagnosed with mucinous liver cystadenomas or cystadenocarcinoma between 1994 and 2009 were included. Pathology specimens of patients who had undergone resection were reviewed for OS. Furthermore, in human embryos, morphology of the peritoneal epithelium and the position of the gonads in relation to the embryonic liver, pancreas and spleen were examined. Results: 15 surgically treated patients (13 female, 2 male) with hepatic tumors were eventually diagnosed with mucinous liver cystadenomas (12) or cystadenocarcinomas (3). OS was present in all female patients with mucinous cystadenoma or cystadenocarcinoma. The 2 male patients were rediagnosed as intraductal papillary mucinous neoplasm (IPMN) or cystadenocarcinoma with features of IPMN. In human embryos, preceding their ‘descent’, the gonads are situated directly under the diaphragm, dorsal to the liver, the tail of the pancreas and the spleen, but separated from these organs by the peritoneal cavity. In contrast to the peritoneal epithelium elsewhere, the cells covering the gonads show an activated morphology. Conclusion: For the diagnosis of mucinous liver cystadenoma, the presence of OS is prerequisite. This may be explained by the common origin of cystadenoma and OS in epithelial cells that cover the embryonic gonads in early fetal life.
Focal Nodular Hyperplasia and Hepatic Adenoma: Epidemiology and Pathology
Authors: Maillette de Buy Wenniger Lucas , Terpstra Valeska , Beuers Ulrich
Published: March 2010

Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) represent the most frequent non-vascular benign liver tumors. They are often asymptomatic. The widespread use of high-resolution imaging modalities leads to an increase of incidental detection of FNH and HA. Physicians are thus increasingly confronted with these formerly rarely recognized conditions, stressing the need for concise but adequate information on the optimal clinical strategies for these patients. FNH is the most common non-vascular benign tumor of the liver. It probably arises as a polyclonal, hyperplastic response to a locally disturbed blood flow. It is typically found in asymptomatic women. Histologically, FNH can be described as a focal form of cirrhosis. Complications of FNH are extremely rare and surgical resection is generally not advised. HA is a rare monoclonal, but benign liver tumor primarily found in young females using estrogen-containing contraceptives. Although its exact etiology is unknown, a direct link between sex steroid exposure and the uncontrolled hepatocellular growth is suspected. Complications of HA are spontaneous bleeding and malignant transformation. Withdrawal of estrogen treatment and excision of large tumors (>5 cm) are established therapeutic strategies. In conclusion, although FNH and HA are reasonably well-described clinical and histopathological entities, their epidemiology and pathophysiology need to be further unraveled.
Malignant Transformation of Liver Adenoma: An Analysis of the Literature
Authors: Farges Olivier , Dokmak Safi
Published: March 2010

As adenoma in other locations, hepatic adenoma (HA) may transform into hepatocellular carcinoma (HCC) and hepatocyte dysplasia is most probably the intermediate step between both conditions. Malignant HA may appear as microscopic or macroscopic areas of HCC within the HA. These areas are typically well differentiated and without vascular extension or satellite nodules. AFP measurements are not reliable as they are usually normal. The risk of malignant transformation of HA cannot be reliably quantified yet. Several series are concordant to show that approximately 5% of patients whose HA have been resected had pathological evidence of HCC within their HA. This figure however does not take into account fully transformed HA where evidence of the preexisting benign lesion might have disappeared. The risk of malignant transformation is correlated with the diameter of the HA and it is very unusual when it is <5 cm and the same holds true for patients with multiple HA. These results suggest that small HA could be safely observed as they are also at low risk of bleeding. These conclusions might not apply to male patients who are at lower risk of HA, except in specific conditions, but appear to be at a much higher risk of malignant changes.
Diagnosis and Treatment of Hepatocellular Adenoma in the Netherlands: Similarities and Differences
Authors: van Aalten S.M. , Terkivatan T. , de Man R.A. , van der Windt D.J. , Kok N.F.M. , Dwarkasing R. , IJzermans J.N.M.
Published: March 2010

Background: The diagnosis of hepatocellular adenoma (HA) has a great impact on the lives of young women and may pose clinical dilemmas to the clinician since there are no standardized protocols to follow. We aimed to establish expert opinions on diagnosis and treatment of HA by collecting data from a nationwide questionnaire in the Netherlands. Methods: A questionnaire was sent to 20 Dutch hospitals known to offer hepatologic and surgical experience on liver tumours. Results: 17 hospitals (85%) responded to the questionnaire. Annually, a median of 52 patients presented with a solid liver tumour. In 15 (88%) hospitals, hepatic adenomas were diagnosed with contrast-enhanced, multiphase spiral CT or MRI. In 2 (12%) hospitals, histology was required as part of a management protocol. Surveillance after withdrawal of oral contraceptives was the initial policy in all clinics. MRI, CT or ultrasound was used for follow-up. Criteria for surgical resection were a tumour size >5 cm and abdominal complaints. In 5 (29%) hospitals, patients were dismissed from follow-up after surgery. In complex cases (e.g. large, multiple or centrally localized lesions, a wish for pregnancy), the treatment policy was highly variable. Pregnancy was not discouraged in 15 hospitals, but in 11 (65%) of these, strictly defined conditions were noted: frequent follow-up, peripheral tumour localization that makes surgery easier if necessary, stable tumour size, and a good informed consent. Conclusion: The management of HAs in the Netherlands is rather uniform, except in complex cases in which multiple factors may influence policy.
Genome-Wide Linkage Scan Maps ETINPH Gene to Chromosome 19q12–13.31
Authors: Zhang Jun , Carr Christopher W. , Rigamonti Daniele , Badr Ahmed
Published: March 2010

Objective: Essential tremor (ET), one of the most common neurological disorders, comprises uncontrollable tremor, usually in the upper extremities. Idiopathic normal pressure hydrocephalus (iNPH) features ventricular enlargement in the absence of elevated intracranial pressure; its three cardinal symptoms are gait impairment, incontinence, and dementia. iNPH is among the most common medical problems in the older population. To date, the genetic etiologies of ET and iNPH remain largely elusive. Methods: We previously identified a large kindred in which the affected members developed ET in adolescence or young adulthood and iNPH when elderly, in that case called ETINPH. Employing two different genotyping microarrays and two- or multipoint linkage analysis strategies, genome-wide linkage scans were performed. Results: We mapped the ETINPH locus to chromosome 19q12–13.31. Fine-mapping in this region revealed a maximum two-point lod score of 2.8 at rs2023865 and a maximum multipoint lod score of 17.9 at rs9304878. By haplotype construction, a (conservatively) approximately 17-cM critical region from SNP rs11084582 to SNP rs7258420 was defined. This region contains several neuronal genes that constitute tantalizing etiological candidates for ETINPH. Conclusion: The importance of uncovering the genetic etiology of this disorder is irrefutable, as such a discovery could offer valuable insights into ET, iNPH, and related neurological conditions.
Vascular Calcification and Cardiovascular Outcome in Dialysis Patients: The Role of Gene Polymorphisms
Authors: Cozzolino Mario , Biondi Maria Luisa , Galassi Andrea , Cusi Daniele , Brancaccio Diego , Gallieni Maurizio
Published: March 2010

Vascular calcification and accelerated atherosclerosis are major causes of death in hemodialysis (HD) patients. Epigenetic mechanisms of gene regulation may be crucial determinants of cellular behavior in uremic conditions, determining an increased risk of cardiovascular morbidity and mortality. The common polymorphisms on different gene promoters have been related to increased coronary artery calcification and associated with cardiovascular outcome in HD population. In this review, we reported the gene polymorphisms of different proteins as negative prognostic risk factors for all-cause mortality in HD patients, independent of traditional risk factors. These data may have important implications for better understanding the pathogenesis of the increased mortality in this population.
Sevelamer Decreases Systemic Inflammation in Parallel to a Reduction in Endotoxemia
Authors: Stinghen A.E.M. , Gonçalves S.M. , Bucharles S. , Branco F.S. , Gruber B. , Hauser A.B. , Pecoits-Filho R.
Published: March 2010

Introduction: Uremic toxins play a pivotal role in the development of systemic complications of chronic kidney disease (CKD), which are largely mediated by the activation of the immune system. Triggers of inflammation in CKD are largely unknown and strategies aiming to reduce circulating ligands that could start the inflammatory response are potentially important. In the present study, we investigated the impact of sevelamer hydrochloride treatment in reducing endotoxemia and inflammation in a group of hemodialysis (HD) patients. Material and Methods: HD patients, who were converted from calcium carbonate treatment to sevelamer according to KDOQI guidelines, were included and prospectively followed for 6 months. Systemic inflammation was evaluated by serum ultra-high-sensitivity C-reactive protein (hsCRP) using an automated immunoturbidimetric assay. Endotoxin was measured using Limulus amebocyte lysate chromogenic endpoint assay. All the analyses were performed immediately before conversion and after 6 months of treatment. Results: After the exclusion of patients discontinuing the treatment, 20 patients (mean dialysis time 12 ± 4 months on HD, age 52 ± 2 years, 38% males, 11% diabetics) were included in the analysis. No significant changes were observed in Ca, P and PTH levels, while a reduction in cholesterol levels was seen. Plasma concentration of hsCRP and endotoxin significantly decreased after 6 months of conversion to sevelamer compared with baseline. Conclusion: We conclude that sevelamer treatment leads to a decrease in hsCRP levels, which was accompanied by a parallel decrease in endotoxemia, suggesting that endotoxemia may contribute to the systemic inflammation in HD patients, which was partially reduced by the use of sevelamer.
The Influence of Drinking Pattern, at Individual and Aggregate Levels, on Alcohol-Related Negative Consequences
Authors: Astudillo M. , Kuntsche S. , Graham K. , Gmel G.
Published: March 2010

Aim: To determine the extent drinking patterns (at the individual and country level) are associated with alcohol-related consequences over and above the total alcohol the person consumes. Methods: Hierarchical linear models were estimated based on general population surveys conducted in 18 countries participating in the GENACIS project. Results: In general, the positive association between drinking pattern scores and alcohol-related consequences was found at both the individual and country levels, independent of volume of drinking. In addition, a significant interaction effect indicated that the more detrimental the country’s drinking pattern, the less steep the association between the volume of drinking and its consequences. Conclusion: Drinking patterns have an independent impact on consequences over and above the relationship between volume and consequences.
Estimating Peak Work Rate during Incremental Cycle Ergometry from the 6-Minute Walk Distance: Differences between Reference Equations
Authors: Holland A.E. , Hill K. , Alison J.A. , Luxton N. , Mackey M.G. , Hill C.J. , Jenkins S.C.
Published: March 2010

Background: Prescription of an appropriate exercise training intensity is critical to optimise the outcomes of pulmonary rehabilitation; however, prescribing cycle ergometry training is challenging if peak work is unknown. Recently two studies reported regression equations which allow estimation of peak cycle work rate from the 6-minute walk distance (6MWD) in chronic obstructive pulmonary disease (COPD). Objectives: To compare estimates of peak work and target training work rate (60% peak) obtained from these equations. Methods: Sixty-four (38 male) subjects, mean ± SD age 70 ± 8 years and FEV1 49 ± 18% predicted with COPD performed the 6-minute walk test according to a standardised protocol. Estimates of peak work were obtained using the published equations and agreement was examined using Bland and Altman plots. Results: Mean 6MWD was 376 ± 86 m compared to 464 ± 110 m and 501 ± 83 m in samples used to derive the equations. There was substantial variation in estimates of peak work between equations (range 1–75 Watts difference) with a coefficient of variation of 35%. Differences were greater in men than in women (p < 0.001). The Luxton equation predicted higher peak work than the Hill equation in younger subjects and at work rates over 50 Watts. Estimated training work rate differed by more than 20 Watts in 18 subjects (28%). Conclusions: This comparison of reference equations for predicting peak cycle work rate from 6MWD indicates substantial variation between methods that differs systematically across the range of work rates. Further research is required to validate the equations and assess their utility for exercise prescription in pulmonary rehabilitation.
Permeabilitätsunterschiede neugebildeter Hornhautgefässe für FITC-Dextrane
Authors: Chioralia G. , Salminen L. , Baurmann H. , Dragomirescu V.
Published: March 2010

3 weeks after NaOH cauterization of rat corneas, the newly formed vessels were angiographically investigated by means of FITC dextran fractions. An angiographic picture similar to that of fluorescein Na was observed after intravenous administration of FD 3. A minimum diffusion of FD 40 could only be detected in the area of the distal terminal loops of the newly formed corneal vessels. FD 70 and FD 150 showed an angiographically similar behaviour with no diffusion in the whole area of neovascularization.
Dorsal (Posterior) Versus Medial Approach for the Surgical Repair of Popliteal Artery Aneurysms
Authors: Bisdas Theodosios , Paraskevas Kosmas I. , Pichlmaier Maximilian , Wilhelmi Matthias , Haverich Axel , Teebken Omke Enno
Published: March 2010

The surgical approach-of-choice for the management of popliteal artery aneurysms (PAAs) remains controversial. We compared the results of the medial (MA) and dorsal (posterior) surgical approach (DA). Fifty patients (44 males/6 females; median age [range]: 59 [49-84] years) treated for 58 atherosclerotic PAAs were studied (MA: 29 PAAs; DA: 29 PAAs). The 3-year graft patency rates were higher after DA compared with MA (76% vs 52%, respectively), but the difference was not significant (P = .056). There were no differences between the 2 approaches in amputation, restenosis, reoperation, and wound infection rates. Dorsal approach and the MA may be alternative approaches with similar long-term results. Due to the controversial results reported so far, a meta-analysis may be necessary to establish the surgical approach-of-choice. Future studies should take into account additional factors, other than the surgical technique, when assessing outcome (eg, preoperative statin use, age, and emergency vs routine surgery).
Morality, Self-Control, Deterrence, and Drug Use
Authors: Gallupe Owen , Baron Stephen W.
Published: March 2010

Utilizing a sample of homeless street youth, the authors apply Wikström’s situational action theory (SAT) to explaining drug use. The article examines the assertion that morality is the most important factor in explaining crime and that self-control and deterrence are key factors in understanding criminal behavior only at moderate levels of morality. Results reveal that morality has a strong effect on hard but not soft drug use, whereas the impact of deterrence on both forms of behavior is stronger than self-control. The proposed conditioning effects outlined in SAT do not have significant associations with drug use. Implications for the theory and avenues for future research are offered.
Altered Fibroblast Proliferation and Apoptosis in Diabetic Gingival Wounds
Authors: Desta T. , Li J. , Chino T. , Graves D.T.
Published: March 2010

Although it is known that diabetes impairs oral wound healing, relatively little is known about the cellular parameters affected, particularly in connective tissue. This study investigated the hypothesis that diabetes impairs connective tissue formation in healing gingiva, and that impaired healing is associated with factors that decrease fibroblast numbers. Full-thickness wounds were created in the palatal gingiva of type 1 and type 2 diabetic and normoglycemic mice. Five days after wounding, diabetic mice had less epithelial wound coverage, less new connective tissue formation, and reduced fibroblast density (p < 0.05). This occurred with increased numbers of caspase-3- and TUNEL-positive fibroblasts, decreased fibroblast proliferation, increased nuclear translocation of the pro-apoptotic transcription factor FOXO1, and increased numbers of polymorphonuclear leukocytes, all of which were significant (p < 0.05). The results suggest that diabetes may decrease fibroblast numbers through increased apoptosis and reduced proliferation, both of which may be mediated through increased activation of FOXO1.
Contingent Intellectual Amateurism, or, the Problem With Evidence-Based Research
Authors: Silk Michael L. , Bush Anthony , Andrews David L.
Published: March 2010

Given the amalgam of neo-liberal, neo-scientist and neo-conservative forces that frame higher education_safeguarding science and medicine at the expense of arts, humanities and the social sciences_the very existence and continuance of the sociology of sport is imperiled perhaps more than ever. In this moment, and not surprisingly, the epistemological corroborator of these forces is once again championed; there has been an aggressive push towards _science_ defined by evidence based programmes, policies and practices (EBR) as the sole and legitimate avenue for academic survival. Heralded as the _gold_ standard of academic research, and forged through university-industry-government partnerships, the evidence based research mantra emphasizes a shift towards corporate principles of efficiency, accountability and profit maximization. As such, within this paper, we discuss the creeping EBR-based epistemological orthodoxy that is seeping into the critical sociological study of sport, arguing that it threatens to neuter the political and critical potentialities of our field. We propose that pandering to EBR, compromises everything that critical sporting intellectuals strive for and believe in; it is a powerful virus of sorts that speaks against our ontological, axiological, epistemological, methodological and political approaches and offers nothing but collusion with, and explicit support for, existing regimes of power.
The Role of Cyprus in the Arabi Revolt and the Resulting Egyptian Campaign of 1882
Authors: Panayiotou Maria
Published: March 2010

This paper looks at British policy in the Mediterranean in the late nineteenth century, and the importance and role of Cyprus as an island under British administration at that time. Specifically, it aims to investigate the neglected role of Cyprus during the Arabi revolt and ensuing Egyptian campaign in 1882. In order to highlight this less-examined aspect, it examines the reasons why Cyprus had not been transformed into a suitable naval station by 1882. It also looks at the effect of the lack of military facilities on the island’s use, and the politicians’ perception of the usefulness of Cyprus during these events in Egypt, vis-à-vis the reaction of the British and Cyprus press.
Political Theater Censorship in Nineteenth-Century France in Comparative European Perspective
Authors: Goldstein Robert Justin
Published: March 2010

Nineteenth-century French political theater censorship was fundamentally in the mainstream of continental European drama censorship, yet it also reflected unique French characteristics. As elsewhere, because theater was viewed as so important during this era of European history, stage censorship occupied a huge amount of the time and energy of French officials and especially focused on proposed texts that were feared as threatening the existing political, legal and class order. Moreover, given the especial fear of the poor and illiterate throughout Europe after the French revolution, and the far greater access of the ‘dark masses’ to the stage as compared with print media, both French authorities and their European counterparts paid particular attention to productions presented in venues which especially attracted the lower classes. Although resistance to the theater censorship began earlier and was more intense in France than elsewhere, French resistance techniques were quite similar to those used elsewhere. However, French theater censorship reflected the unique characteristics of the country in three ways: (1) because the theater was probably even more important in France than anywhere else in continental Europe, censorship also seems to have been more important, and it clearly engaged the attention of both the authorities and the opposition more than elsewhere; (2) the centralized-authoritarian-bureaucratic nature of nineteenth-century French politics was reflected in highly centralized censorship decisions which were not subject to court appeal, unlike in several other European countries; and (3) the extraordinary instability of nineteenth-century French politics was completely and accurately reflected in French theater censorship history, which, to a degree unknown elsewhere in Europe, was repeatedly abolished, reinstated, tightened or loosened in a clear echo of broader political currents.
Potemkin in Spain? British Unofficial Missions of Investigation to Spain during the Civil War
Authors: García Hugo
Published: March 2010

This paper seeks to contribute to the debate on the international repercussions of the Spanish Civil War by analysing the numerous British missions of investigation that visited both sides during the conflict. Drawing on the travellers’ own accounts and the documents from Spanish and British archives among other sources, it argues that these missions were in fact organized tours, first used as propaganda by Republicans and their Comintern advisers, and subsequently copied by Nationalists on a more limited basis. Although some involved genuinely impartial observers, most of the visitors were already committed to the cause they pretended to investigate. Spanish war tourism thus almost invariably succeeded in producing favourable publicity for both sides, yet failed to affect the majority of the British people, who were influenced primarily by their Government’s neutral stance. Regardless of its outcome, the experience aptly illustrates the extent to which persuasion and commitment determined foreign responses to the conflict.