bluuebunny/crossref_metadata_2025_split huggingface dataset:
Method to improve the mitigative effectiveness of a series of check dams against debris flows
Authors: Osti Rabindra , Egashira Shinji 
Published: September 2008

AbstractThe advance of technology has led to more competent countermeasures, but lives and properties still continue to suffer from water‐induced disasters, such as floods, landslides, and debris flows. To increase the effectiveness of counter systems, improved methods of planning and designing such systems are prerequisite. This paper describes briefly a methodological approach for predicting debris flow characteristics, and proposes techniques for evaluating and improving the mitigative effectiveness of check dams against debris flows in steep mountain torrents. Additionally, a non‐dimensional parameter, namely potential storage volume, is introduced to generalize the evaluation processes. As an example, the 1999 debris‐flow event in the San Julian River, Venezuela, is chosen for discussion. The paper also proposes a method of evaluating the control function of a series of check dams as well as the criteria for the selection of their sizes, numbers and locations. It is hoped that this work will help to determine which combinations of check dams will fit best together for the optimal control of debris flows and available resources in any river basin. Copyright © 2008 John Wiley & Sons, Ltd.
A two‐dimensional inverse model to identify transmissivity in an anisotropic aquifer
Authors: Wu Shih‐Ching , Tan Yih‐Chi , Chen Chu‐Hui , Lin Shien‐Tsung , Ke Kai‐Yuan 
Published: September 2008

AbstractThis study suggested a numerical model using the Tabu search algorithm along with the Adjoint State method to identify the hydrogeological characteristics of an anisotropic groundwater aquifer. The Tabu search algorithm was applied to identify the anisotropic transmissivity components to avoid a local optimum. Then, the Adjoint State method was used to calculate the sensitivity of the parameters in order to increase the efficiency of the optimization. For an anisotropic and homogeneous aquifer, results showed that the optimal procedure presented combining the Tabu search algorithm and the Adjoint State method might successfully identify the values of the transmissivity components. If the duration of the pumping test was long enough (12‐h pumping test), the value of the transmissivity components could be optimized with type‐curve, straight‐line, and Tabu search methods, along with the Adjoint State methods. If the duration of the pumping test was short (0·5‐h pumping test), the Tabu search method, along with the Adjoint State method proposed herein, might successfully optimize the transmissivity components. For an anisotropic but heterogeneous aquifer, results showed that the suggested optimal procedure still successfully identified the values of the transmissivity components. Copyright © 2008 John Wiley & Sons, Ltd.
Biophysical and biochemical characterization of a liposarcoma‐derived recombinant MnSOD protein acting as an anticancer agent
Authors: Mancini Aldo , Borrelli Antonella , Schiattarella Antonella , Aloj Luigi , Aurilio Michela , Morelli Franco , Pica Alessandra , Occhiello Antonella , Lorizio Roberto , Mancini Roberto , Sica Alessandro , Mazzarella Lelio , Sica Filomena , Grieco Paolo , Novellino Ettore , Pagnozzi Daniela , Pucci Piero , Rommelaere Jean 
Published: September 2008

AbstractA recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild‐type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N‐terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium‐labelled synthetic peptide. The labelled peptide permeated MCF‐7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I‐ and 131I‐labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro‐apoptotic mechanism. © 2008 Wiley‐Liss, Inc.
Original triazine inductor of new specific molecular targets, with antitumor activity against nonsmall cell lung cancer
Authors: Moreau Dimitri , Jacquot Catherine , Tsita Polyxeni , Chinou Ioanna , Tomasoni Cristophe , Juge Marcel , Antoniadou‐Vyza Ekaterini , Martignat Lionel , Pineau Alain , Roussakis Christos 
Published: September 2008

AbstractDespite our growing insight into carcinogenesis, treatment of tumors, especially nonsmall cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. Drug discovery efforts have historically focused on the search for compounds that modulate the protein products of genes. Current drug therapy targets only a few hundred endogenous targets, mainly proteins, such as receptors and enzymes. But now, the interest in specifically targeting RNA is increasing, both for target validation and/or therapeutic purposes. In this regard, our work was concerned with the induction of new molecular targets correlated to a cytostatic effect on NSCLC cell line, after treatment with a new triazin named A190. The in vitro study of cell cycle and apoptosis induction demonstrated the antiproliferative potential of this new compounds, and the use of quantitative RT‐PCR analysis permit to display an original mechanism of action involving 2 genes: HEF1 and B2. The antitumor effect was also confirmed by the good results in vivo on nude mice xenografts. © 2008 Wiley‐Liss, Inc.
MicroRNA alterations in head and neck squamous cell carcinoma
Authors: Chang Steven S. , Jiang Wei Wen , Smith Ian , Poeta Luana M. , Begum Shahnaz , Glazer Chad , Shan Shannon , Westra William , Sidransky David , Califano Joseph A. 
Published: September 2008

AbstractMicroRNAs (mirs) are small noncoding RNA molecules (∼22 nucleotides) that regulate posttranscriptional gene expression. Currently, there has not been a comprehensive study of their role in primary head and neck squamous cell carcinoma (HNSCC). To determine the role of mirs in HNSCC, we screened for altered microRNA expression in HNSCC primary tissue and cell lines. We then further tested the functional impact of alterations of specific mirs. An initial screening of 4 primary HNSCC, 4 normal mucosal controls and 4 HNSCC cell lines was analyzed for mature microRNA expression by microarray. Significance was determined using significance analysis of microarrays (SAM). Nine microRNAs were found by SAM to be upregulated or downregulated in tumor tissue including mir‐21, let‐7, 18, 29c, 142‐3p, 155, 146b (overexpressed) and 494 (underexpressed). Mir‐21 was validated by qRT‐PCR. Functional validation by growth assays was performed, further validating mir‐21. Transfection of mir‐21 into JHU‐011 and JHU‐012 cell lines showed a 39% increase in cell growth at 72 hr relative to controls (p < 0.05). Transfection of the inhibitor into JHU‐O12 cell lines showed a 92% decrease in cell growth relative to controls at 72 hr (p < 0.05). In addition, flow cytometry analysis of JHU‐012 cells 48 hr after mir‐21 inhibitor transfection showed a statistically significant increase in cytochrome c release and increased apoptosis. These differentially expressed microRNAs may be of interest as potential novel oncogenes and tumor suppressor genes in HNSCC. Mir‐21 is a putative oncogenic microRNA in head and neck cancer. © 2008 Wiley‐Liss, Inc.
Distinct CpG island methylation profiles and BRAF mutation status in serrated and adenomatous colorectal polyps
Authors: Kim Yong Ho , Kakar Sanjay , Cun Lisa , Deng Guoren , Kim Young S. 
Published: September 2008

AbstractA subset of colorectal cancers with CpG island methylator phenotype‐high (CIMP‐H) is frequently associated with MSI and BRAF V600E mutation. Since limited data are available on different histological types of colorectal polyps, we compared the pattern and the frequency of promoter methylation, CIMP‐H, MSI, KRAS and BRAF V600E mutations and the relationship among these molecular parameters and the clinicopathologic characteristics in 110 serrated polyps (48 hyperplastic polyps, 32 sessile serrated adenomas and 30 serrated adenomas) and 32 tubular adenomas using 7 commonly used tumor‐associated gene loci. No significant difference in the frequency of overall methylation frequency (86% vs. 100%) and CIMP‐H (39% vs. 28%) between serrated polyps and tubular adenomas was observed, but proximally located serrated polyps showed more frequent methylation at 5 of 7 loci examined, and were more likely to be CIMP‐H (62% vs. 22%). MGMT methylation was more common in tubular adenomas while MLH1 and HIC1 were more frequently methylated in serrated polyps. BRAF mutation was frequently present in all types of serrated polyps (80%), but was absent in tubular adenomas and was not associated with CIMP or MSI status. These results show comparable frequencies of promoter methylation of tumor‐associated genes and CIMP‐H, but distinct differences in gene‐specific or colonic site‐specific methylation profiles occur in serrated polyps and tubular adenomas. BRAF mutation occurs independently of CIMP and MSI in all types of serrated polyps and may serve as a marker of serrated pathway of colorectal carcinogenesis. © 2008 Wiley‐Liss, Inc.
A panel of p16INK4A, MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma
Authors: Hoevenaars Brigiet M. , van der Avoort Irene A.M. , de Wilde Peter C.M. , Massuger Leon F.A.G. , Melchers Willem J.G. , de Hullu Joanne A. , Bulten Johan 
Published: September 2008

AbstractTwo pathways leading to vulvar squamous cell carcinoma (SCC) exist. The expression of proliferation‐ and cell‐cycle‐related biomarkers and the presence of high‐risk (hr) HPV might be helpful to distinguish the premalignancies in both pathways. Seventy‐five differentiated vulvar intra‐epithelial neoplasia (VIN)‐lesions with adjacent SCC and 45 usual VIN‐lesions (32 solitary and 13 with adjacent SCC) were selected, and tested for hr‐HPV DNA, using a broad‐spectrum HPV detection/genotyping assay (SPF10‐LiPA), and the immunohistochemical expression of MIB1, p16INK4A and p53. All differentiated VIN‐lesions were hr‐HPV‐ and p16‐negative and in 96% MIB1‐expression was confined to the parabasal layers. Eighty‐four percent exhibited high p53 labeling indices, sometimes with parabasal extension. Eighty percent of all usual VIN‐lesions were hr‐HPV‐positive, p16‐positive, MIB1‐positive and p53‐negative. Five (of seven) HPV‐negative usual VIN lesions, had an expression pattern like the other HPV‐positive usual VIN lesions. In conclusion, both pathways leading to vulvar SCC have their own immunohistochemical profile, which can be used to distinguish the 2 types of VIN, but cannot explain differences in malignant potential. © 2008 Wiley‐Liss, Inc.
Intraperitoneal administration of a small interfering RNA targeting nuclear factor‐kappa B with paclitaxel successfully prolongs the survival of xenograft model mice with peritoneal metastasis of gastric cancer
Authors: Inoue Masashi , Matsumoto Sachiko , Saito Hiroaki , Tsujitani Shunichi , Ikeguchi Masahide 
Published: September 2008

AbstractActivation of nuclear factor‐kappa B (NF‐κB) has been detected in various malignant tumors, including gastric carcinoma, and is associated with tumor growth, metastasis, resistance to chemotherapeutic agents and poor prognosis. Therefore, NF‐κB is a potential target for antitumor therapy. In this study, we used a small interfering RNA (siRNA) to knockdown NF‐κB p65 expression and determined whether intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel was effective for treating peritoneal metastasis of gastric cancer. Western blot analysis revealed that NF‐κB p65 expression was diminished by NF‐κB p65 siRNA. Apoptotic cells were increased after transfection of NF‐κB p65 siRNA compared with control siRNA in the treatment with paclitaxel. In a murine xenograft model, abundant fluorescence was observed on the surface of intraperitoneal nodules of gastric cancer after siRNA administration. Moreover, intraperitoneal administration of NF‐κB p65 siRNA reduced NF‐κB expression in intraperitoneal nodules of gastric cancer. Finally, mice treated by intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel survived for a significantly longer time than mice treated by intraperitoneal administration of paclitaxel alone (p = 0.0002). Taken together, the present results demonstrate that intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel inhibited cancer growth in mice with peritoneal metastasis of gastric cancer. Therefore, intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel may provide a breakthrough in the treatment of peritoneal metastasis of gastric cancer. © 2008 Wiley‐Liss, Inc.
Isosilibinin inhibits advanced human prostate cancer growth in athymic nude mice: Comparison with silymarin and silibinin
Authors: Deep Gagan , Raina Komal , Singh Rana P. , Oberlies Nicholas H. , Kroll David J. , Agarwal Rajesh 
Published: September 2008

AbstractEarlier studies have shown the cancer chemopreventive efficacy of silymarin and its semi‐purified constituent silibinin against prostate cancer (PCa), but the efficacy of other constituents of silymarin is largely unknown. In the present study, we assessed the in vivo growth inhibitory efficacy of one such constituent isosilibinin (a 50:50 mixture of isosilybin A and isosilybin B) in comparison with silymarin and silibinin in human PCa DU145 xenograft in athymic nude mice. Isosilibinin feeding (200 mg/kg body weight per day) significantly inhibited the growth of xenograft after 53 days of treatment (p ≤ 0.005), which was equally or slightly better effective than silymarin and silibinin, respectively. Treatment with isosilibinin, silymarin and silibinin was stopped after 53 days and tumor volume was measured till 77 days. After 24 days of treatments withdrawal, tumor volume remain decreased, however, it was statistically significant only with isosilibinin (p ≤ 0.05), suggesting its prolonged effect. Biomarker analysis showed that isosilibinin, silymarin and silibinin treatment for 53 days significantly inhibited the immunoreactivity for proliferating cell nuclear antigen (PCNA), microvessel density (CD31) and vascular endothelial growth factor along with significant increase in apoptotic cell population. The PCNA levels in tumors remained significantly low even after 24 days of treatments withdrawal. Western blot analysis of tumor tissue suggested that these flavonolignan formulations differentially alter the expression of cell cycle regulatory molecules, cyclins and Cdks. Overall, the results of present study suggest that isosilibinin has comparatively better efficacy against PCa and should be further analyzed for its clinical utility. © 2008 Wiley‐Liss, Inc.
Heparanase induces VEGF C and facilitates tumor lymphangiogenesis
Authors: Cohen‐Kaplan Victoria , Naroditsky Inna , Zetser Anna , Ilan Neta , Vlodavsky Israel , Doweck Ilana 
Published: September 2008

AbstractHeparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains, a class of glycosaminoglycans abundantly present in the extracellular matrix and on the cell surface. Heparanase activity is strongly implicated in tumor angiogenesis and metastasis attributed to remodeling of the subepithelial and subendothelial basement membranes. We hypothesized that similar to its proangiogenic capacity, heparanase is also engaged in lymphangiogenesis and utilized the D2‐40 monoclonal antibody to study lymphangiogenesis in tumor specimens obtained from 65 head and neck carcinoma patients. Lymphatic density was analyzed for association with clinical parameters and heparanase staining. We provide evidence that lymphatic vessel density (LVD) correlates with head and neck lymph node metastasis (N‐stage, p = 0.007) and inversely correlates with tumor cell differentiation (p = 0.007). Notably, heparanase staining correlated with LVD (p = 0.04) and, moreover, with VEGF C levels (p = 0.01). We further demonstrate that heparanase overexpression by epidermoid, breast, melanoma and prostate carcinoma cells induces a 3‐ to 5‐fold elevation in VEGF C expression in vitro and facilitates tumor xenograft lymphangiogenesis in vivo, whereas heparanase gene silencing was associated with decreased VEGF C levels. These findings suggest that heparanase plays a unique dual role in tumor metastasis, facilitating tumor cell invasiveness and inducing VEGF C expression, thereby increasing the density of lymphatic vessels that mobilize metastatic cells. © 2008 Wiley‐Liss, Inc.
Tumor microenvironment: Modulation by decorin and related molecules harboring leucine‐rich tandem motifs
Authors: Goldoni Silvia , Iozzo Renato V. 
Published: September 2008

AbstractDecorin, the prototype member of the small leucine‐rich proteoglycans, resides in the tumor microenvironment and affects the biology of various types of cancer by downregulating the activity of several receptors involved in cell growth and survival. Decorin binds to and modulates the signaling of the epidermal growth factor receptor and other members of the ErbB family of receptor tyrosine kinases. It exerts its antitumor activity by a dual mechanism: via inhibition of these key receptors through their physical downregulation coupled with attenuation of their signaling, and by binding to and sequestering TGFβ. Decorin also modulates the insulin‐like growth factor receptor and the low‐density lipoprotein receptor‐related protein 1, which indirectly affects the TGFβ receptor pathway. When expressed in tumor xenograft‐bearing mice or injected systemically, decorin inhibits both primary tumor growth and metastatic spreading. In this review, we summarize the latest reports on decorin and related molecules that are relevant to cancer and bring forward the idea of decorin as an anticancer therapeutic and possible prognostic marker for patients affected by various types of tumors. We also discuss the role of lumican and LRIG1, a novel cell growth inhibitor homologous to decorin. © 2008 Wiley‐Liss, Inc.
The methylenetetrahydrofolate reductase C677T mutation induces cell‐specific changes in genomic DNA methylation and uracil misincorporation: A possible molecular basis for the site‐specific cancer risk modification
Authors: Sohn Kyoung‐Jin , Jang Hyeran , Campan Mihaela , Weisenberger Daniel J. , Dickhout Jeffrey , Wang Yi‐Cheng , Cho Robert C. , Yates Zoe , Lucock Mark , Chiang En‐Pei , Austin Richard C. , Choi Sang‐Woon , Laird Peter W. , Kim Young‐In 
Published: September 2008

AbstractThe C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased risk of colon cancer although it may increase the risk of breast cancer. This polymorphism is associated with changes in intracellular folate cofactors, which may affect DNA methylation and synthesis via altered one‐carbon transfer reactions. We investigated the effect of this mutation on DNA methylation and uracil misincorporation and its interaction with exogenous folate in further modulating these biomarkers of one‐carbon transfer reactions in an in vitro model of the MTHFR 677T mutation in HCT116 colon and MDA‐MB‐435 breast adenocarcinoma cells. In HCT116 cells, the MTHFR 677T mutation was associated with significantly increased genomic DNA methylation when folate supply was adequate or high; however, in the setting of folate insufficiency, this mutation was associated with significantly decreased genomic DNA methylation. In contrast, in MDA‐MB‐435 cells, the MTHFR 677T mutation was associated with significantly decreased genomic DNA methylation when folate supply was adequate or high and with no effect when folate supply was low. The MTHFR 677T mutation was associated with a nonsignificant trend toward decreased and increased uracil misincorporation in HCT116 and MDA‐MB‐435 cells, respectively. Our data demonstrate for the first time a functional consequence of changes in intracellular folate cofactors resulting from the MTHFR 677T mutation in cells derived from the target organs of interest, thus providing a plausible cellular mechanism that may partly explain the site‐specific modification of colon and breast cancer risks associated with the MTHFR C677T mutation. © 2008 Wiley‐Liss, Inc.
Induction of the lysosomal apoptosis pathway by inhibitors of the ubiquitin‐proteasome system
Authors: Berndtsson Maria , Beaujouin Melanie , Rickardson Linda , Havelka Aleksandra Mandic , Larsson Rolf , Westman Jacob , Liaudet‐Coopman Emmanuelle , Linder Stig 
Published: September 2008

AbstractThe lysosomal apoptosis pathway is a potentially interesting therapeutic target. Since apoptosis involving the lysosomal pathway has been described to involve cathepsins, we screened a drug library for agents that induce cathepsin‐dependent apoptosis. Using pharmacological inhibitors and siRNA, we identified 2 structurally related agents (NSC687852 and NSC638646) that induced cathepsin D‐dependent caspase‐cleavage activity in human breast cancer cells. Both agents were found to induce the mitochondrial apoptosis pathway. NSC687852 and NSC638646 were found to inhibit the activity of ubiquitin isopeptidases and to induce the accumulation of high‐molecular‐mass ubiquitins in cells. We show that 3 other inhibitors of the proteasome degradation pathway induce lysosomal membrane permeabilization (LMP) and that cathepsin‐D siRNA inhibits apoptosis induced by these agents. We conclude that a screen for cathepsin‐dependent apoptosis‐inducing agents resulted in the identification of ubiquitin isopeptidase inhibitors and that proteasome inhibitors with different mechanisms of action induce LMP and cathepsin D‐dependent apoptosis. © 2008 Wiley‐Liss, Inc.