bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of PAR‐4, a pro‐apoptotic gene, in pancreatic tumors harboring K‐ras mutation
Authors: Ahmed Mansoor M. , Sheldon David , Fruitwala Mushtaq A. , Venkatasubbarao Kolaparthi , Lee Eun Y. , Gupta Seema , Wood Craig , Mohiuddin Mohammed , Strodel William E. 
Published: September 2007

AbstractOncogenic ras is known to inhibit cell death and growth inhibitory genes and activate prosurvival genes. Proapoptotic gene PAR‐4, has been found to be downregulated by oncogenic ras. Since pancreatic tumors harbor a high incidence of K‐ras point mutations, we hypothesized that oncogenic K‐ras might influence the function and expression of PAR‐4. PAR‐4 expression levels were analyzed in 4 established pancreatic tumor cell lines, 10 normal pancreatic tissues, 44 frozen tumor tissues and 25 paraffin‐embedded pancreatic adenocarcinoma samples by Real Time RT‐PCR, Western blot analysis and immunohistochemistry. K‐ras mutational status was analyzed by allele‐specific oligonucleotide‐hybridization. Expression levels of PAR‐4 were correlated with the K‐ras mutational status and clinical characteristics. Further, modulation of endogenous PAR‐4 was tested by transiently expressing oncogenic ras in a wild‐type K‐ras pancreatic cancer cell line, BxPC‐3. Three cell lines with K‐ras mutations showed low levels of PAR‐4 when compared to a normal pancreatic tissue. Of 44 frozen tumors, 16 showed appreciable upregulation of Par mRNA and 27 showed significant downregulation of PAR‐4 mRNA when compared to normal pancreatic tissue and 1 had levels equivalent to normal pancreatic tissue. Of 25 paraffin‐embedded tumors, 9 showed downregulation of PAR‐4 protein and this downregulation of PAR‐4 correlated significantly with K‐ras mutational status (p < 0.00002). In addition, the presence of PAR‐4 mRNA or protein expression in pancreatic tumors correlated with prolonged survival. Transient overexpression of oncogenic ras in wild‐type K‐ras BxPC‐3 cells significantly downregulated the endogenous PAR‐4 protein levels and conferred accelerated growth. Thus, downregulation or loss of PAR‐4 expression by oncogenic ras may provide a selective survival advantage for pancreatic tumors, through inhibition of proapoptotic pathway mediated by PAR‐4. © 2007 Wiley‐Liss, Inc.
Tobacco smoking and cancer: A meta‐analysis
Authors: Gandini Sara , Botteri Edoardo , Iodice Simona , Boniol Mathieu , Lowenfels Albert B. , Maisonneuve Patrick , Boyle Peter 
Published: September 2007

AbstractWe conducted a systematic meta‐analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case‐control studies, 75 cohorts and 2 nested case‐control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for ‘current’ and/or ‘former’ smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73–12.11), laryngeal (RR = 6.98; 95% CI: 3.14–15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86–15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63–4.84) and oral (RR = 3.43; 95% CI: 2.37–4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies. © 2007 Wiley‐Liss, Inc.
c‐Abl activates p38 MAPK independently of its tyrosine kinase activity: Implications in cisplatin‐based therapy
Authors: Galan‐Moya Eva M. , Hernandez‐Losa Javier , Aceves Luquero Clara I. , de la Cruz‐Morcillo Miguel A. , Ramírez‐Castillejo Carmen , Callejas‐Valera Juan L. , Arriaga Angel , Aranburo Antonio Fernandez , Cajal Santiago Ramón y , Silvio Gutkind J. , Sánchez‐Prieto Ricardo 
Published: September 2007

AbstractActivation of p38 MAPK is a critical requisite for the therapeutics activity of the antitumor agent cisplatin. In this sense, a growing body of evidences supports the role of c‐Abl as a major determinant of p38 MAPK activation, especially in response to genotoxic stress when triggered by cisplatin. Here, we demonstrate that p38 MAPK activation in response to cisplatin does not require the tyrosine kinase activity of c‐Abl. Indeed, c‐Abl can activate the p38 MAPK signaling pathway by a mechanism that is independent of its tyrosine kinase activity, but that instead involves the ability of c‐Abl to increase the stability of MKK6. Similar results were obtained in chronic myeloid leukemia‐derived cell lines, in which a chimeric Bcr/Abl protein mimics the effects of c‐Abl overexpression on p38 MAPK activation. These findings may explain why a clinically used c‐Abl inhibitor, imatinib mesylate, fails to inhibit the p38 MAPK pathway alone or in combination with cisplatin, and provide evidence of a novel signaling mechanism in which these antitumor agents act. © 2007 Wiley‐Liss, Inc.
The activities of progesterone receptor isoform A and B are differentially modulated by their ligands in a gene‐selective manner
Authors: Leo Joyce C.L. , Lin Valerie C.L. 
Published: September 2007

AbstractIt is known that progesterone receptor (PR) isoform A (PR‐A) and isoform B (PR‐B) may mediate different effects of progesterone. The objective of this study was to determine if the functions of PR isoforms also vary in response to different PR modulators (PRM). The effects of 7 synthetic PRM were tested in MDA‐MB‐231 cells engineered to express PR‐A, PR‐B, or both PR isoforms. The effects of progesterone were similar in cells expressing PR‐A or PR‐B in which it inhibited growth and induced focal adhesion. On the other hand, synthetic PRM modulated the activity of the PR isoforms differently. RU486, CDB4124, 17α‐hydroxy CDB4124 and VA2914 exerted agonist activities on cell growth and adhesion via PR‐B. Via PR‐A, however, these compounds displayed agonist effect on cell growth but induced stellate morphology which was distinct from the agonist's effect. Their dual properties via PR‐A were also displayed at the gene expression level: the compounds acted as agonists on cell cycle genes but exhibited antagonistic effect on cell adhesion genes. Introduction of ERα by adenoviral vector to these cells did not change PR‐A or PR‐B mediated effect of PRM radically, but it causes significant cell rounding and modified the magnitudes of the responses to PRM. The findings suggest that the activities of PR isoforms may be modulated by different PRM through gene‐specific regulatory mechanisms. This raises an interesting possibility that PRM may be designed to be PR isoform and cellular pathway selective to achieve targeted therapy in breast cancer. © 2007 Wiley‐Liss, Inc.
Socio‐demographic determinants of participation in mammography screening
Authors: Euler‐Chelpin My von , Olsen Anne Helene , Njor Sisse , Vejborg Ilse , Schwartz Walter , Lynge Elsebeth 
Published: September 2007

AbstractOur objective was to use individual data on socio‐demographic characteristics to identify predictors of participation in mammography screening and control to what extent they can explain the regional difference. We used data from mammography screening programmes in Copenhagen, 1991–1999, and Funen, 1993–2001, Denmark. Target groups were identified from the Population Register, screening data came from the health authority, and socio‐demographic data from Statistics Denmark. Included were women eligible for at least 3 screens. The crude RR of never use versus always use was 3.21 (95%CI, 3.07–3.35) for Copenhagen versus Funen, and the adjusted RR was 2.55 (95%CI, 2.43–2.67). The adjusted RR for never use among women without contact to a primary care physician was 2.50 (95% CI, 2.31–2.71) and 2.89 (95% CI, 2.66–3.14), and for women without dental care 2.94 (95% CI, 2.77–3.12) and 2.88 (95% CI, 2.68–3.10) for Copenhagen and Funen, respectively. Other important predictive factors for nonparticipation were not being married and not being Danish. In conclusion, to enhance participation in mammography screening programmes special attention needs to be given to women not using other primary health care services. All women in Copenhagen, irrespective of their socio‐demographic characteristics, had low participation. Screening programmes have to find ways to handle this urbanity factor. © 2007 Wiley‐Liss, Inc.
Beyond foreign‐body‐induced carcinogenesis: Impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression
Authors: Okada Futoshi 
Published: September 2007

AbstractForeign‐body‐induced carcinogenesis is a traditional, maybe old, way of understanding cancer development. A number of novel approaches are available today to elucidate cancer development. However, there are things we learn from the old, and thus I bring out some examples of various clinical cases and experimental models of foreign‐body‐induced tumorigenesis. What is notable is that the foreign bodies themselves are unrelated to each other, whereas commonly underlying in them is to induce inflammatory reaction, especially stromal proliferation, where those exogenous materials are incorporated and undigested. Such foreign‐body‐induced carcinogenesis is also recognized in the step of tumor progression, the final step of carcinogenesis that tumor cells acquire malignant phenotypes including metastatic properties. And the phenomenon is universally observed in several cell lines of different origins. In this review I would like to show the evidence that tumor development and progression are accelerated inevitably by inflammation caused from foreign bodies, and that reactive oxygen species derived from inflammatory cells are one of the most important genotoxic mediators to accelerate the process. © 2007 Wiley‐Liss, Inc.
Inflammation and cancer: An ancient link with novel potentials
Authors: Perwez Hussain S. , Harris Curtis C. 
Published: September 2007

AbstractInfection and chronic inflammation contribute to about 1 in 4 of all cancer cases. Mediators of the inflammatory response, e.g., cytokines, free radicals, prostaglandins and growth factors, can induce genetic and epigenetic changes including point mutations in tumor suppressor genes, DNA methylation and post‐translational modifications, causing alterations in critical pathways responsible for maintaining the normal cellular homeostasis and leading to the development and progression of cancer. Recent discovery of an interaction between microRNAs and innate immunity during inflammation has further strengthened the association between inflammation and cancer. © 2007 Wiley‐Liss, Inc.
Axial specification in mice: Ten years of advances and controversies
Authors: Rivera‐Perez Jaime A. 
Published: September 2007

AbstractThe definitive axes of the mouse embryo can be unequivocally identified in embryos dissected at 5.5 days of gestation. However, how and when are these axes established remains an open question. At pre‐implantation stages, different approaches have been aimed at determining if events occurring in the zygote influence the geometrical arrangement of the blastocyst. An intense debate has focused on whether the mouse embryo is a pre‐patterned or a regulative structure. At post‐implantation stages, the efforts have been concentrated in understanding how extra‐embryonic tissues affect the formation of the primitive streak, the caudal marker of the anteroposterior axis. Here I summarize the last 10 years of research in this field. J. Cell. Physiol. 213:654–660. © 2007 Wiley‐Liss, Inc.
FVTD—integral equation hybrid for Maxwell's equations
Authors: Firsov Dmitry K. , LoVetri Joe 
Published: September 2007

AbstractA new hybrid finite‐volume time‐domain integral equation (FVTD/IE) algorithm for the solution of Maxwell's Equations on unstructured meshes of arbitrary flat‐faceted volume elements is presented. A time‐domain IE‐based numerical algorithm is applied on the boundary of the computational domain to determine the incoming fluxes for the boundary facets of the mesh. This method is a global grid‐truncation technique similar to the method previously introduced for the finite‐difference time‐domain scheme by Ziolkowski et al. The three main advantages of this IE truncation method are that (1) it allows geometrical objects to be located (almost) arbitrarily close to the mesh boundaries without compromising the physics of the problem, (2) it couples the physics of unconnected meshes so that distant scatterers can be surrounded by their own local mesh, thus reducing total mesh size, and (3) the same IE formulation can be used to compute electromagnetic field values at points outside the mesh. Currently, the main disadvantage is that an acceleration scheme for performing the IE update, which requires integrating field components on an interior surface at a retarded time, is not available. Computational results are presented for the scattering from a perfectly electrical conducting sphere and compared numerically with the analytic time‐domain solution as well as the solution obtained using a large spherical outer mesh boundary with local absorbing boundary conditions. Results are excellent and show almost no reflections from the mesh boundary even when the observation point is located close to the corner of the cubically shaped outside mesh boundary. Results are also presented and validated for the scattering from two objects that are contained inside their own unconnected meshes. Copyright © 2007 John Wiley & Sons, Ltd.
Growth‐compromised HSV‐2 vector ΔRR protects from N‐methyl‐D‐aspartate‐induced neuronal degeneration through redundant activation of the MEK/ERK and PI3‐K/Akt survival pathways, either one of which overrides apoptotic cascades
Authors: Laing Jennifer M. , Golembewski Erin K. , Wales Samantha Q. , Liu Juan , Jafri M. Samir , Yarowsky Paul J. , Aurelian Laure 
Published: September 2007

AbstractWe have previously shown that intrastriatal injection of ΔRR, the growth‐compromised herpes simplex virus type 2 (HSV‐2) vector for the antiapoptotic protein ICP10PK, prevents apoptosis caused by the excitotoxin N‐methyl‐D‐aspartate (NMDA) in a mouse model of glutamatergic neuronal cell death (Golembewski et al. [2007] Exp. Neurol. 203:381–393). Because apoptosis regulation is stimulus and cell type specific, our studies were designed to examine the mechanism of ΔRR‐mediated neuroprotection in striatal neurons. Organotypic striatal cultures (OSC) that retain much of the synaptic circuitry of the intact striatum were infected with ΔRR or a growth‐compromised HSV‐2 vector that lacks ICP10PK (ΔPK) and examined for neuroprotection‐associated signaling. The mutated ICP10 proteins (p175 and p95) were expressed in 70–80% of neurons from ΔRR‐ and ΔPK‐infected cultures, respectively, as determined by double‐immunofluorescent staining with antibodies to ICP10 and NeuN or GAD65. ΔRR‐ but not ΔPK‐treated OSC were protected from NMDA‐induced apoptosis, as verified by ethidium homodimer staining, TUNEL, caspase‐3 activation, and poly(AD‐ribose) polymerase (PARP) cleavage. Neuroprotection was through ICP10PK‐mediated activation of the survival pathways MEK/ERK and PI3‐K/Akt, up‐regulation of the antiapoptotic proteins Bag‐1 and Bcl‐2, and phosphorylation (inactivation) of the proapoptotic protein Bad. It was blocked by the MEK inhibitor U0126 or the PI3‐K inhibitor LY294002, suggesting that either pathway can prevent NMDA‐induced apoptosis. The data indicate that ΔRR‐delivered ICP10PK stimulates redundant survival pathways that override proapoptotic cascades. ΔRR is a promising gene therapy platform against glutamatergic cell death. © 2007 Wiley‐Liss, Inc.
Low‐dose morphine induces hyperalgesia through activation of Gαs, protein kinase C, and l‐type Ca2+ channels in rats
Authors: Esmaeili‐Mahani Saeed , Shimokawa Noriaki , Javan Mohammad , Maghsoudi Nader , Motamedi Fereshteh , Koibuchi Noriyuki , Ahmadiani Abolhasan 
Published: September 2007

AbstractOpioids can induce analgesia and also hyperalgesia in humans and in animals. It has been shown that systemic administration of morphine induced a hyperalgesic response at an extremely low dose. However, the exact mechanism(s) underlying opioid‐induced hyperalgesia has not yet been clarified. Here, we have investigated cellular events involved in low‐dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 μg i.t.) could elicit hyperalgesia as assessed by the tail‐flick test. Gαs mRNA and protein levels increased significantly following exposure to the hyperalgesic dose of morphine. Furthermore, morphine at an analgesic dose (20 μg i.t.) significantly decreased cAMP levels in the dorsal half of the lumbar spinal cord, whereas the tissue cAMP levels were not affected by morphine treatment at a hyperalgesic dose. Intrathecal administration of nifedipine, an L‐type calcium channel blocker, antagonized the hyperalgesia induced by the low‐dose of morphine. Furthermore, pretreatment with the selective protein kinase C (PKC) inhibitor chelerytrine resulted in prevention of the morphine‐induced hyperalgesia. KT 5720, a specific inhibitor of protein kinase A (PKA), did not show any effect on low‐dose morphine‐induced hyperalgesia. These results indicate a role for Gαs, the PLC‐PKC pathway, and L‐type calcium channels in intrathecal morphine‐induced hyperalgesia in rats. Activation of ordinary Gαs signaling through cAMP levels did not appear to play a major role in the induction of hyperalgesia by low‐dose of morphine. © 2007 Wiley‐Liss, Inc.
Aquaporin‐4 water channels in enteric neurons
Authors: Thi Mia M. , Spray David C. , Hanani Menachem 
Published: September 2007

AbstractAquaporin‐4 is a water channel predominantly found in astrocytes in the central nervous system and is believed to play a critical role in the formation and maintenance of the blood–brain barrier and in water secretion from the brain. As enteric glial cells were found to share several similarities with astrocytes, we hypothesized that enteric glia might also contain aquaporin‐4. We used immunohistochemistry to identify aquaporin‐4 in the myenteric and submucosal plexuses of the mouse and the rat colon. We found that subpopulations of neurons in both enteric plexuses were positively labeled for human aquaporin‐4. Double staining of the enteric ganglia with antibodies to the neuronal marker neurofilament–heavy chain 100 and to aquaporin‐4 showed that a minority of myenteric neurons were aquaporin‐4 positive (about 12% in the mouse and 13% in the rat). In contrast, in the submucosal plexus significant numbers of neurons were positive for aquaporin‐4 (about 79% in both the mouse and the rat). Double labeling for aquaporin‐4 and for the glial marker glial fibrillary acidic protein verified that glial cells were not immunoreactive to aquaporin‐4. We further confirmed our findings with additional aquaporin‐4 antibodies and Western blot analysis. We found that, in addition to expressing aquaporin‐4, the myenteric plexus and, to a greater extent, the submucosal plexus both expressed aquaporin‐1. We conclude that neurons rather than glial cells contain aquaporin‐4 in the colonic enteric plexuses. It is known that submucosal neurons control transport processes in the intestinal mucosa, and the high percentage of aquaporin‐4‐postive submucosal neurons suggests that aquaporin‐4 contributes to this function. © 2007 Wiley‐Liss, Inc.
Pharmacological inhibition of GSK‐3 is not strictly correlated with a decrease in tyrosine phosphorylation of residues 216/279
Authors: Simón D. , Benitez M. J. , Gimenez‐Cassina A. , Garrido J. J. , Bhat R. V. , Díaz‐Nido J. , Wandosell F. 
Published: September 2007

AbstractRecent evidence suggests that intramolecular autophosphorylation is responsible for the tyrosine phosphorylation (pY) of residues 279 or 216 of glycogen synthase kinase–3 (GSK‐3α or β), an event that appears to play an important role in regulating this kinase. This provocative hypothesis was based on the capacity of certain nonselective GSK‐3 inhibitors to alter both the activity of GSK‐3 and its pY. Inhibitors of GSK‐3 are not always capable of preventing this tyrosine phosphorylation, which may require an extended period of time. For example, although lithium chloride inhibits GSK‐3 activity, this inhibition does not alter its pY content. Furthermore, even when GSK‐3 activity is impaired, GSK‐3 pY can still be modified by physiological or pharmacological agents. Taken together, these data indicate that GSK‐3 kinase activity is not necessarily correlated with the extent of GSK‐3 pY. We hypothesized that some as‐yet‐unidentified tyrosine kinases and phosphatases may also regulate this kinase. © 2007 Wiley‐Liss, Inc.
Raman spectroscopy of halogen‐containing carbonates
Authors: Frost Ray L. , Dickfos Marilla J. 
Published: September 2007

AbstractRaman spectroscopy complemented with infrared spectroscopy has been used to study a series of selected natural halogenated carbonates from different origins, including bastnasite, parisite and northupite. The position of CO32− symmetric stretching vibration varies with the mineral composition. An additional band for northupite at 1107 cm−1 is observed. Raman spectra of bastnasite, parisite and northupite show single bands at 1433, 1420 and 1554 cm−1, respectively, assigned to the ν3 (CO3)2− asymmetric stretching mode. The observation of additional Raman bands for the ν3 modes for some halogenated carbonates is significant in that it shows distortion of the CaO6 octahedron. No ν2 Raman bending modes are observed for these minerals. The band is observed in the infrared spectra, and multiple ν2 modes at 844 and 867 cm−1 are observed for parisite. A single intense infrared band is found at 879 cm−1 for northupite. Raman bands are observed forthe carbonate ν4 in‐phase bending modes at 722 cm−1 for bastnasite, 736 and 684 cm−1 for parisite and 714 cm−1 for northupite. Multiple bands are observed in the OH stretching region for selected bastansites and parisites, indicating the presence of water and OH units in the mineral structure. The presence of such bands brings into question the actual formula of these halogenated carbonate minerals. Copyright © 2007 John Wiley & Sons, Ltd.
Dissociation of C6F5SO3Li in two organic solvents with different dielectric constants: a Raman spectroscopic study
Authors: Hirankumar G. , Iojoiu C. , Alloin F. , Sanchez J. Y. , Pagnier T. 
Published: September 2007

AbstractOrganic solutions of lithium pentafluorobenzene sulfonate (C6F5SO3Li) with varying molalities in N,N‐dimethyl formamide (DMF) and triethyleneglycol dimethylether (triglyme) were investigated by Raman spectroscopy. Spectral decomposition in the νs(SO3) stretching region showed bands characteristic of free anions, ion pairs and various aggregates. The relative fraction of each species has been followed as a function of salt molality. In DMF, free anions dominate, while in triglyme ion pairs dominate, in accordance with the solvent dielectric constant. Copyright © 2007 John Wiley & Sons, Ltd.