bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultraviolet B Irradiation Affects Resistance of Rainbow Trout (Oncorhynchus mykiss) Against Bacterium Yersinia ruckeri and Trematode Diplostomum spathaceum
Authors: Markkula S. Eveliina , Karvonen Anssi , Salo Harri , Tellervo Valtonen E. , Ilmari Jokinen E. 
Published: July 2007

AbstractUltraviolet B (UVB) radiation is known to have various effects on the immune system of fish, but the effect on the actual disease resistance has remained largely unknown. Here we studied the effect of UVB on the resistance of rainbow trout (Oncorhynchus mykiss) against a bacterium Yersinia ruckeri, the causative agent of enteric red mouth disease, and a trematode parasite Diplostomum spathaceum, which causes cataracts in fish. The fish were exposed to UVB irradiation seven times in 14 days, and inoculated intraperitoneally with Y. ruckeri on day 5 after the first irradiation. On day 2 postinfection (p.i.), the number of viable bacteria in the kidney was lower in UVB‐exposed than in unexposed fish. However, on day 8 p.i., UVB‐irradiated fish had not been able to clear remaining Y. ruckeri effectively, and had a slightly higher bacterial load than controls. A similar, although not significant, effect was seen in the bacterial numbers in spleen. In the other experiment, fish were exposed to UVB for six consecutive days and then exposed to D. spathaceum. A significantly higher number of parasites was detected in the eyes of irradiated fish, indicating reduced resistance against the pathogen. Furthermore, UVB‐irradiation altered the immunological and hematological parameters of fish, which also verified the immunomodulatory potential of UVB in the present study.
Quenching of Singlet Molecular Oxygen, O2(1Δg), by Dipyridamole and Derivatives
Authors: Oliveira Marilene Silva , Lima Michelle , Severino Divinomar , Baptista Maurício da Silva , Mascio Paolo Di , Tabak Marcel 
Published: July 2007

AbstractDipyridamole (DIP) is known for its vasodilating and antiplatelet activity, exhibiting also a potent antioxidant effect, strongly inhibiting lipid peroxidation. This effect has been studied in mitochondria and a correlation between the DIP derivatives’ structure, the ability to bind to micelles and biological activity has been suggested. In the present work, the quenching of singlet molecular oxygen, O2(1Δg), by DIP and RA47 and RA25 derivatives was analyzed in acetonitrile (ACN) and aqueous acid solutions. Laser flash photolysis excitation of methylene blue (MB) was made at 532 nm and monomol light emission of O2(1Δg) was monitored at 1270 nm. Bimolecular quenching constants in ACN are consistent with an efficient physical quenching, presenting values a bit lower than the diffusion limit (kt = 3.4–6.8 × 108 m−1 s−1). The quenching process probably occurs via reversible charge transfer with the formation of an exciplex. Calculation of ΔGet associated with O2(1Δg) quenching corroborates with uncompleted electron transfer. In aqueous acid solutions (pH = 3.0), the kt values for DIP and derivatives are 20‐fold smaller when compared with ACN. The electrochemical properties of DIP in ACN are characterized by two consecutive one‐electron processes with half‐wave oxidation potentials of 0.30 and 0.67 V vs saturated calomel electrode (SCE). However, in an aqueous acid medium, a single oxidation wave is observed involving a two‐electron process (0.80 V vs SCE). Therefore, O2(1Δg) quenching is consistent with electrochemical data.
Open versus closed kinetic chain exercises for patellar chondromalacia
Authors: Bakhtiary A H , Fatemi E 
Published: July 2007

Subject:Conservative treatment of patellar chondromalacia has been the subject of several studies. One recommended treatment is a strengthening exercise of the quadriceps muscle, which may be performed in closed or open kinetic chains. This study was designed to compare the effect of straight leg raise (SLR) and semi-squat exercises on the treatment of patellar chondromalacia, which has not been done to date.Material and methods:32 female university students with a diagnosis of patellar chondromalacia were randomly assigned to two experimental groups: SLR and semi-squat exercise. Before starting exercise protocols, Q angle, maximal isometric voluntary contraction force (MIVCF) of quadriceps, crepitation, circumference of thigh 5 and 10 cm above the patella and patellofemoral pain according to the visual analogue scale (VAS) were assessed. Both groups then followed a 3-week programme of quadriceps muscle strengthening exercises (SLR or semi-squat) starting with 20 exercises twice a day and increasing each session by 5 exercises every 2 days. All measurements were repeated at the end of each week and then again 2 weeks after the 3-week exercise programme.Results:Reduced Q angle (mean differences (SD) 0.8 (0.3), p = 0.016) and crepitation (19.9 (8.5), p = 0.04), and an increase in the MIVCF of the quadriceps (15.8 (5.6), p = 0.01) and thigh circumference (1.5 (0.3), p = 0.001) were found in semi-squat group compared with SLR group. However, patellofemoral pain was decreased significantly in both groups.Conclusion:The results of this study indicate that semi-squat exercises (closed kinetic chain) are more effective than SLR exercise (open kinetic chain) in the treatment of patellar chondromalacia. More studies are needed to investigate the long-term effect of these types of exercise.
Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injuryThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Singla Dinender K. , Kaur Kuljeet , Sharma Anita K. , Dhingra Sanjiv , Singal Pawan K. 
Published: July 2007

The present study examines whether a subchronic probucol treatment of rats offers protection against ischemia–reperfusion (IR) injury in isolated perfused hearts. Sprague–Dawley rats were treated every second day per week with probucol (cumulative dose 120 mg/kg body mass, i.p.) for 4 weeks. In the probucol group, baseline myocardial antioxidant enzyme, glutathione peroxidase (GSHPx), activity was increased (p < 0.05), whereas superoxide dismutase (SOD) and catalase (CAT) activities were not changed. Baseline oxidative stress, as indicated by the myocardial lipid peroxidation, was less (p < 0.05) in the probucol group. Isolated hearts were subjected to 60 min global I and 20 min R. Recovery of the contractile function in globally ischemic hearts upon reperfusion was 36% in untreated group and 74% in the probucol group. After IR, GSHPx and CAT activities were significantly (p < 0.05) higher in the probucol group compared with the control group, whereas SOD did not change. Lipid peroxidation owing to IR was significantly less in the probocol group. These data suggest that probucol treatment improves endogenous antioxidant reserve and protects against increased oxidative stress following IR injury.
Hydrogen peroxide causes cardiac dysfunction independent from its effects on matrix metalloproteinase-2 activationThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: León Hernando , Bautista-López Norma , Sawicka Jolanta , Schulz Richard 
Published: July 2007

Hydrogen peroxide (H2O2) causes cardiac dysfunction through multiple mechanisms. As oxidative stress can activate matrix metalloproteinases (MMPs) and, in particular, MMP-2 activity is associated with oxidative stress injury in the heart, we hypothesized that MMP-2 activation by H2O2in isolated rat hearts contributes to cardiac dysfunction in this model. Isolated working rat hearts were perfused at 37 °C with a recirculating Krebs–Henseleit buffer ± 5 mmol/L pyruvate, known to protect hearts from oxidative stress. H2O2(300 µmol/L) was added as a single bolus after 20 min of equilibration, and cardiac function was monitored for 60 min. MMPs activities in both the heart and perfusate samples were assessed by gelatin zymography. Tissue high energy phosphates were analysed by HPLC. The actions of 2 MMP inhibitors, doxycycline (75 µmol/L) or Ro 31-9790 (3 µmol/L), were also assessed. H2O2at 300 µmol/L produced a rapid decline in cardiac mechanical function, which was maximal at 5 min. A peak in perfusate MMP-2 activity was also observed at 5 min. The deleterious effect of H2O2on cardiac function was abolished by pyruvate but not by the MMPs inhibitors. This study suggests that in intact hearts, H2O2induces contractile dysfunction independent of MMPs activation.
Ral-GTPase interacts with the β1 subunit of Na+/K+-ATPase and is activated upon inhibition of the Na+/K+pumpThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Bhullar Rajinder P. , Clough Richard R. , Kanungo Juddy , Elsaraj Sherif M. , Grujic Ognjen 
Published: July 2007

Na+/K+-ATPase functions as both an ion pump and a signal transducer. Cardiac glycosides partially inhibit Na+/K+-ATPase, causing activation of multiple interrelated growth pathways via the Na+/K+-ATPase/c-Src/epidermal growth factor receptor complex. Such pathways include Ras/MEK/ERK and Ral/RalGDS cascades, which can lead to cardiac hypertrophy. In search of novel Ral-GTPase binding proteins, we used RalB as the bait to screen a human testes cDNA expression library using the yeast 2-hybrid system. The results demonstrated that 1 of the RalB interacting clones represented the C-terminal region of the β1 subunit of Na+/K+-ATPase. Further analysis using the yeast 2-hybrid system and full-length β1 subunit of Na+/K+-ATPase confirmed the interaction with RalA and RalB. In vitro binding and pull-down assays demonstrated that the β1 subunit of Na+/K+-ATPase interacts directly with RalA and RalB. Ral-GTP pull-down assays demonstrated that short-term ouabain treatment of A7r5 cells, a rat aorta smooth muscle cell line, caused activation of Ral GTPase. Maximal activation was observed 10 min after ouabain treatment. Ouabain-mediated Ral activation was inhibited upon the stimulation of Na+/K+-ATPase activity by Ang II. We propose that Ral GTPase is involved in the signal transducing function of Na+/K+-ATPase and provides a possible molecular mechanism connecting Ral to cardiac hypertrophy during diseased conditions.
Patterns of Known and Novel Small RNAs in Human Cervical Cancer
Authors: Lui Weng-Onn , Pourmand Nader , Patterson Bruce K. , Fire Andrew 
Published: July 2007

AbstractRecent studies suggest that knowledge of differential expression of microRNAs (miRNA) in cancer may have substantial diagnostic and prognostic value. Here, we use a direct sequencing method to characterize the profiles of miRNAs and other small RNA segments for six human cervical carcinoma cell lines and five normal cervical samples. Of 166 miRNAs expressed in normal cervix and cancer cell lines, we observed significant expression variation of six miRNAs between the two groups. To further show the biological relevance of our findings, we examined the expression level of two significantly varying miRNAs in a panel of 29 matched pairs of human cervical cancer and normal cervical samples. Reduced expression of miR-143 and increased expression of miR-21 were reproducibly displayed in cancer samples, suggesting the potential value of these miRNAs as tumor markers. In addition to the known miRNAs, we found a number of novel miRNAs and an additional set of small RNAs that do not meet miRNA criteria. [Cancer Res 2007;67(13):6031–43]
High-Mobility Group A1 Proteins Inhibit Expression of Nucleotide Excision Repair Factor Xeroderma Pigmentosum Group A
Authors: Adair Jennifer E. , Maloney Scott C. , Dement Gregory A. , Wertzler Kelsey J. , Smerdon Michael J. , Reeves Raymond 
Published: July 2007

Abstract
Cells that overexpress high-mobility group A1 (HMGA1) proteins exhibit deficient nucleotide excision repair (NER) after exposure to DNA-damaging agents, a condition ameliorated by artificially lowering intracellular levels of these nonhistone proteins. One possible mechanism for this NER inhibition is down-regulation of proteins involved in NER, such as xeroderma pigmentosum complimentation group A (XPA). Microarray and reverse transcription-PCR data indicate a 2.6-fold decrease in intracellular XPA mRNA in transgenic MCF-7 cells overexpressing HMGA1 proteins compared with non–HMGA1-expressing cells. XPA protein levels are also ∼3-fold lower in HMGA1-expressing MCF-7 cells. Moreover, whereas a &gt;2-fold induction of XPA proteins is observed in normal MCF-7 cells 30 min after UV exposure, no apparent induction of XPA protein is observed in MCF-7 cells expressing HMGA1. Mechanistically, we present both chromatin immunoprecipitation and promoter site-specific mutagenesis evidence linking HMGA1 to repression of XPA transcription via binding to a negative regulatory element in the endogenous XPA gene promoter. Phenotypically, HMGA1-expressing cells exhibit compromised removal of cyclobutane pyrimidine dimer lesions, a characteristic of cells that express low levels of XPA. Importantly, we show that restoring expression of wild-type XPA in HMGA1-expressing cells rescues UV resistance comparable with that of normal MCF-7 cells. Together, these data provide strong experimental evidence that HMGA1 proteins are involved in inhibiting XPA expression, resulting in increased UV sensitivity in cells that overexpress these proteins. Because HMGA1 proteins are overexpressed in most naturally occurring cancers, with increasing cellular concentrations correlating with increasing metastatic potential and poor patient prognosis, the current findings provide new insights into previously unsuspected mechanisms contributing to tumor progression. [Cancer Res 2007;67(13):6044–52]
Endothelin Receptor Type B Counteracts Tenascin-C–Induced Endothelin Receptor Type A–Dependent Focal Adhesion and Actin Stress Fiber Disorganization
Authors: Lange Katrin , Kammerer Martial , Hegi Monika E. , Grotegut Stefan , Dittmann Antje , Huang Wentao , Fluri Erika , Yip George W. , Götte Martin , Ruiz Christian , Orend Gertraud 
Published: July 2007

Abstract
Tenascin-C, an extracellular matrix molecule of the tumor-specific microenvironment, counteracts the tumor cell proliferation–suppressing effect of fibronectin by blocking the integrin α5β1/syndecan-4 complex. This causes cell rounding and stimulates tumor cell proliferation. Tenascin-C also stimulates endothelin receptor type A (EDNRA) expression. Here, we investigated whether signaling through endothelin receptors affects tenascin-C–induced cell rounding. We observed that endothelin receptor type B (EDNRB) activation inhibited cell rounding by tenascin-C and induced spreading by restoring expression and function of focal adhesion kinase (FAK), paxillin, RhoA, and tropomyosin-1 (TM1) via activation of epidermal growth factor receptor, phospholipase C, c-Jun NH2-terminal kinase, and the phosphatidylinositol 3-kinase pathway. In contrast to EDNRB, signaling through EDNRA induced cell rounding, which correlated with FAK inhibition and TM1 and RhoA protein destabilization in the presence of tenascin-C. This occurred in a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase–dependent manner. Thus, tumorigenesis might be enhanced by tenascin-C involving EDNRA signaling. Inhibition of tenascin-C in combination with blocking both endothelin receptors could present a strategy for sensitization of cancer and endothelial cells toward anoikis. [Cancer Res 2007;67(13):6163–73]
Folate Receptor–Specific Antitumor Activity of EC131, a Folate-Maytansinoid Conjugate
Authors: Reddy Joseph A. , Westrick Elaine , Santhapuram Hari K.R. , Howard Stephen J. , Miller Michael L. , Vetzel Marilynn , Vlahov Iontcho , Chari Ravi V.J. , Goldmacher Victor S. , Leamon Christopher P. 
Published: July 2007

Abstract
EC131, a new folate receptor (FR)–targeted drug conjugate, was prepared by covalently attaching the vitamin folic acid (FA) to a potent microtubule-inhibiting agent, maytansinoid DM1, via an intramolecular disulfide bond. When tested on cells in culture, EC131 was found to retain high affinity for FR-positive cells and to provide FR-specific cytotoxicity with an IC50 in the low nanomolar range. The activity of EC131 was completely blocked in the presence of an excess of free FA, and no activity was detected against FR-negative cells. When evaluated against s.c. FR-positive M109 tumors in BALB/c mice, EC131 showed marked antitumor efficacy. Furthermore, this therapeutic effect occurred in the apparent absence of weight loss or noticeable organ tissue degeneration. In contrast, no significant antitumor activity was observed in EC131-treated animals that were codosed with an excess of FA, thus demonstrating the targeted specificity of the in vivo activity. EC131 also showed marked antitumor activity against FR-positive human KB tumors, but not against FR-negative A549 tumors, in nude mice with no evidence of systemic toxicity during or after the therapy. In contrast, therapy with the free maytansinoid drug (in the form of DM1-S-Me) proved not to be effective against the KB model when administered at its maximum tolerated dose (MTD). Taken together, these results indicate that EC131 is a highly potent agent capable of producing therapeutic benefit in murine tumor models at sub-MTD levels. [Cancer Res 2007;67(13):6376–82]
Adipose Tissue–Derived Human Mesenchymal Stem Cells Mediated Prodrug Cancer Gene Therapy
Authors: Kucerova Lucia , Altanerova Veronika , Matuskova Miroslava , Tyciakova Silvia , Altaner Cestmir 
Published: July 2007

Abstract
Human adipose tissue–derived mesenchymal stem cells (AT-MSC) are considered to be a promising source of autologous stem cells in personalized cell-based therapies. Tumor tracking properties of MSC provide an attractive opportunity for targeted transgene delivery into the sites of tumor formation. In the present study, we addressed whether the suicide gene introduction into human AT-MSC could produce a tumor-specific prodrug converting cellular vehicle for targeted chemotherapy. We prepared yeast fusion cytosine deaminase::uracil phosphoribosyltransferase gene–expressing cells [cytosine deaminase (CD)–expressing AT-MSC (CD-AT-MSC)] by retrovirus transduction. We explored their therapeutic potential on a model of human colon cancer in the presence of prodrug 5-fluorocytosine (5-FC). Gene manipulation of human AT-MSC did not sensitize CD-AT-MSC to 5-FC, thus overcoming the inherent disadvantage of suicide effect on cellular vehicle. CD-AT-MSC in combination with 5-FC augmented the bystander effect and selective cytotoxicity on target tumor cells HT-29 in direct coculture in vitro. We confirmed directed migration ability of AT-MSC and CD-AT-MSC toward tumor cells HT-29 in vitro. Moreover, we achieved significant inhibition of s.c. tumor xenograft growth by s.c. or i.v. administered CD-AT-MSC in immunocompromised mice treated with 5-FC. We confirmed the ability of CD-AT-MSC to deliver the CD transgene to the site of tumor formation and mediate strong antitumor effect in vivo. Taken together, these data characterize MSC derived from adipose tissue as suitable delivery vehicles for prodrug converting gene and show their utility for a personalized cell-based targeted cancer gene therapy. [Cancer Res 2007;67(13):6304–13]
Requirement for IFN-γ, CD8+ T Lymphocytes, and NKT Cells in Talactoferrin-Induced Inhibition of neu+ Tumors
Authors: Spadaro Michela , Curcio Claudia , Varadhachary Atul , Cavallo Federica , Engelmayer Jose , Blezinger Paul , Pericle Federica , Forni Guido 
Published: July 2007

AbstractWe have previously shown that talactoferrin-alfa (TLF), a recombinant human lactoferrin, is an immunomodulatory protein that is active against implanted tumors, both as a single agent and in combination with chemotherapy. In this study, we show that talactoferrin is active against autochthonous tumors in a transgenic mouse line, which is more analogous to human cancers, and identify key mechanistic steps involved in the anticancer activity of oral TLF. BALB/c mice transgenic for the rat neu (ErbB2) oncogene (BALB-neuT) treated with oral TLF showed a significant delay in carcinogenesis, with 60% tumor protection relative to vehicle-treated mice at week 21. Oral TLF also showed tumor growth inhibition in wild-type BALB/c mice implanted with neu+ mammary adenocarcinoma, with one third displaying a long-lasting or complete response. Oral TLF induces an increase in intestinal mucosal IFN-γ production and an increase in Peyer's patch cellularity, including expansion of CD8+ T lymphocytes and NKT cells, and the enhancement of CD8+ T-cell cytotoxicity. In IFN-γ knockout mice, there is an absence of the TLF-induced Peyer's patch cellularity, no expansion of CD8+ T lymphocytes and NKT cells, and loss of TLF anticancer activity. TLF antitumor activity is also lost in mice depleted of CD8+ T cells and in CD1 knockout mice, which lack NKT activity. Thus, the inhibition of distant tumors by oral TLF seems to be mediated by an IFN-γ–dependent enhancement of CD8+ T- and NKT cell activity initiated within the intestinal mucosa. [Cancer Res 2007;67(13):6425–32]
The RON Receptor Tyrosine Kinase Mediates Oncogenic Phenotypes in Pancreatic Cancer Cells and Is Increasingly Expressed during Pancreatic Cancer Progression
Authors: Thomas Ryan M. , Toney Kenya , Fenoglio-Preiser Cecilia , Revelo-Penafiel Monica P. , Hingorani Sunil R. , Tuveson David A. , Waltz Susan E. , Lowy Andrew M. 
Published: July 2007

AbstractPancreatic cancer is an aggressive disease characterized by rapid growth and early metastasis. The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed and/or constitutively active in several epithelial cancers, but its role in pancreatic cancer is unknown. In this study, we have characterized RON expression in both murine and human pancreatic cancer. Immunoblotting indicates that RON is expressed in pancreatic intraepithelial neoplasia (PanIN), primary, and metastatic cell lines both in the human and mouse. Immunostaining revealed that 93% of high-grade PanIN, 79% of primary, and 83% of metastatic lesions from human pancreatic tissue samples expressed RON, with minimal expression in normal ducts and low-grade PanIN (6% and 18%, respectively). Moreover, we show a dose-dependent effect of hepatocyte growth factor-like protein (HGFL), the RON-specific ligand, on pancreatic cancer cell migration and invasion, which was reversed by RON inhibition. Although stimulation with HGFL had no effect on proliferation, concurrent RON receptor blockade and gemcitabine treatment increased apoptosis of RON-expressing pancreatic cancer cells versus gemcitabine treatment alone. Finally, HGFL stimulation of pancreatic cancer cells resulted in increased expression of phospho-mitogen-activated protein kinase and phospho-Akt. Taken together, these findings suggest that RON receptor signaling may contribute to pancreatic carcinogenesis, and that further investigation is warranted to assess the potential of RON-directed therapies in this deadly disease. [Cancer Res 2007;67(13):6075–82]