bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the mechanism of induction of apoptosis in ovarian carcinoma cells by the conformationally restricted synthetic retinoids CD437 and 4‐HPR
Authors: Holmes William F. , Soprano Dianne Robert , Soprano Kenneth J. 
Published: April 2003

AbstractAll‐trans‐retinoic acid (ATRA) has been shown to inhibit the growth of a number of ovarian tumor cell lines while others have been found to be resistant to retinoid suppression of growth. Interestingly, two synthetic retinoids, CD437 and 4‐HPR, inhibit the growth of both ATRA‐sensitive (CA‐OV‐3) and ATRA‐resistant (SK‐OV‐3) ovarian tumor cells. However, in contrast to ATRA, both induce apoptosis. Our goal was to elucidate the mechanism by which these two synthetic retinoids induce apoptosis in ovarian tumor cells. Since it has been documented that apoptosis induction is often mediated by the activation of a cascade of proteases known as caspases, we initially studied the role of caspases in induction of apoptosis by CD437 and 4‐HPR. We found that both retinoids induced caspase‐3 and caspase‐9 enzyme activity. Furthermore, using caspase specific inhibitors we determined that caspase‐3 and caspase‐9 activity was essential for the induction of apoptosis by these synthetic retinoids since these inhibitors completely blocked CD437 and 4‐HPR induced apoptosis. Interestingly, we found that treatment with bongkriekic acid (BA), a mitochondrial membrane depolarization inhibitor, blocked apoptosis, caspase‐9 activation and caspase‐3 activation induced by both retinoids. Finally, we were able to determine that CD437 treatment induced the translocation of TR3, a nuclear orphan receptor, whereas, 4‐HPR did not. Our results suggest that CD437 and 4‐HPR initially activate separate pathways to induce mitochondrial depolarization but both utilize mitochondrial depolarization, caspase‐9 activation, and caspase‐3 activation in the later stages of apoptosis induction. J. Cell. Biochem. 89: 262–278, 2003. © 2003 Wiley‐Liss, Inc.
Anti‐apoptotic defense of bcl‐2 gene against hydroperoxide‐induced cytotoxicity together with suppressed lipid peroxidation, enhanced ascorbate uptake, and upregulated Bcl‐2 protein
Authors: Saitoh Yasukazu , Ouchida Rika , Kayasuga Atsushi , Miwa Nobuhiko 
Published: April 2003

AbstractAlthough it is well known that Bcl‐2 can prevent apoptosis, the Bcl‐2's anti‐apoptotic mechanism is not fully understood. Here, we investigate the mechanism of oxidant‐induced cell death and to investigate the role of Bcl‐2 in the tert‐butyl hydroperoxide (t‐BuOOH)‐induced oxidant injury in Rat‐1 fibroblasts and their bcl‐2 transfected counterparts, b5 cells. Treatment with t‐BuOOH causes mitochondrial disfunction and induced morphological features consistent with apoptosis more markedly in Rat‐1 cells than in b5 cells. The hydroperoxide t‐BuOOH at concentrations less than 100 nM for as long as 48 h or with higher concentrations (up to 100 μM) for only 3 h induces death in Rat‐1 cells, whereas their bcl‐2 transfectants were significantly resistant to cytotoxicity by both time and all concentration other than 100 μM. The similar results were obtained also for DNA strand cleavages as detected by TUNEL stain. The bcl‐2 transfectants significantly suppressed t‐BuOOH‐induced increases in both lipid peroxidation and caspase‐3 activation 3 and 1 h after t‐BuOOH exposure, respectively, but failed to suppress either caspase‐1 activation or an enhanced production of the intracellular reactive oxygen species (ROS). Intracellular uptake of [1‐14C] ascorbic acid (Asc) into the bcl‐2 transfectants was superior to that into the non‐transfectants always under examined conditions regardless of serum addition to culture medium and cell density. Upregulation of Bcl‐2 proteins was rapidly induced after t‐BuOOH exposure in the transfectants, but not in non‐transfectants, and restored till 24 h to the normal Bcl‐2 level. Thus suppressions of both lipid peroxidation and the subsequent cell death events such as caspase‐3 activation and DNA cleavage were concerned with the inhibitory effects of Bcl‐2 on the t‐BuOOH‐induced cytotoxicity. And some of these events may correlate with Bcl‐2 expression‐induced partial enhanced anti‐oxidant cellular ability including enrichment of intracellular Asc and oxidative stress‐induced upregulation of Bcl‐2 protein. On the other hand, ROS production and caspase‐1 activation were not related to cytoprotection by Bcl‐2. J. Cell. Biochem. 89: 321–334, 2003. © 2003 Wiley‐Liss, Inc.
Proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures: Effects of dexamethasone and calcitriol
Authors: Atmani Hassan , Chappard Daniel , Basle Michel F. 
Published: April 2003

AbstractDuring bone loss, osteoblast population can be replaced by adipose tissue. This apparent reciprocal relationship between decreased bone density and increased fat formation can be explained by an imbalance in the production of bone‐forming and fat‐forming cells in the marrow cavity. Thus, osteoblast and adipocyte pathways seem more closely and inversely related. In the present study, we investigated the effects of dexamethasone (dex) and calcitriol [1,25(OH)2D3] on proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures. Stromal cells were grown in primoculture in presence of dex and subcultivated in presence of dex and/or 1,25(OH)2D3. Total cell proliferation, osteoblast and adipocyte‐cells number, and ‐mRNA specific markers were used to study the effects of hormonal treatment on stromal cells. Total cell proliferation was stimulated by dex and inhibited by 1,25(OH)2D3. Dex increased osteoblast and adipocyte cell population whereas calcitriol decreased bone‐forming cell number and increased fat cell population. The presence of both hormones led to a strong decrease in osteoblastic cells and to a strong increase in adipocytic cell number. Dex induced mRNA osteoblastic markers expression like bone sialoprotein (BSP) and osteocalcin (OC) and an adipocyte marker expression, the fatty acid binding protein aP2. Calcitriol decreased the dex‐induced BSP expression but stimulated slightly OC and aP2 mRNA. The effects of both hormones was to increase strongly OC and aP2 mRNA. These results support that, in rat bone marrow, adipocyte proliferation and differentiation are stimulated by glucocorticoids and calcitriol which act synergically, whereas osteoblastic cell proliferation and differentiation are increased by dex and inhibited by 1,25(OH)2D3. J. Cell. Biochem. 89: 364–372, 2003. © 2003 Wiley‐Liss, Inc.
Developmental expression of the type I diabetes related antigen sulfatide and sulfated lactosylceramide in mammalian pancreas
Authors: Blomqvist Maria , Kaas Anne , Månsson Jan‐Eric , Formby Bent , Rynmark Britt‐Marie , Buschard Karsten , Fredman Pam 
Published: April 2003

AbstractPrevious studies have shown that sulfatide is present and functionally involved in beta cells, and that anti‐sulfatide antibodies (ASA) exist during development of type I diabetes mellitus. To further explore the possible role of sulfatide in type I diabetes, developmental expression was examined in human pancreas and in pancreas of the type I diabetes models BB rat and NOD mouse compared to Lewis rat and BALB/c mouse, respectively. Sulfatide was not only expressed in adult pancreas, but also in human fetal and rodent neonatal pancreas, i.e., during the growing period of the immunological self. Sulfatide had a different expression pattern in human beings and rodents, concerning both the amounts of sulfatide and expression during development. There was no change in the sulfatide fatty acid isoform expression during development. The pancreatic expression of another sulfated glycosphingolipid, sulfated lactosylceramide, indicated that this molecule is a potential fetal/neonatal marker, which was further expressed in the type I diabetic models. In conclusion, these findings give further support to the possibility that sulfatide is a relevant autoantigen in type I diabetes and that sulfated lactosylceramide might function as a potential risk factor for disease development, at least in the animal models. J. Cell. Biochem. 89: 301–310, 2003. © 2003 Wiley‐Liss, Inc.
Endothelial activation by angiotensin II through NFκB and p38 pathways: Involvement of NFκB‐inducible kinase (NIK), free oxygen radicals, and selective inhibition by aspirin
Authors: Costanzo Antonio , Moretti Francesca , Burgio Vito Lelio , Bravi Cristina , Guido Francesco , Levrero Massimo , Puri Pier Lorenzo 
Published: April 2003

AbstractAngiotensin‐II (AII), the dominant effector of the renin–angiotensin system, is involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis. Upregulation of the adhesion molecules VCAM‐1, ICAM‐1, and E‐selectin in endothelial cells by inflammatory cytokines through nuclear factor kappa B (NFκB) activation is implicated in formation and progression of atherosclerotic plaque. Here we show that AII induces NFκB‐dependent transcription in primary endothelial cell lines, leading to the upregulation of ICAM‐1 and VCAM‐1 expression. NFκB activation by AII is mediated by the NFκB‐inducing kinase (NIK), a common mediator of NFκB activation by inflammatory cytokines, such as TNF‐α. However, NFκB stimulation by AII differs from that of TNF‐α since a TNF‐receptor associated factor 2 (TRAF‐2) dominant negative mutant does not prevent AII‐mediated NFκB activation. In analogy with TNF‐α‐dependent activation of NFκB, treatment with either the anti‐oxidant N‐acetyl cysteine (NAC) or the cyclooxygenase (COX) inhibitor acetyl salicylic acid (aspirin), but not indometacin, prevents the induction of NFκB‐dependent transcription by AII. Thus, production of reactive oxygen species, aspirin (asp)‐sensitive enzymes of the arachidonate metabolism, and NIK are common transducers of AII‐ and TNF‐dependent pathways to NFκB. AII also activates the inflammatory p38 kinase in endothelial cells, an effect inhibited by exposure to either NAC or asp. Pharmacological interference of the p38 pathway, with the inhibitor SB 202190, prevented AII‐mediated activation of the NFκB target V‐CAM, without affecting degradation of IκBα. These results support a pro‐inflammatory effect of the vasoactive peptide AII in endothelial cells, through at least two pathways—NFκB and p38—both of which are sensitive to asp and antioxidants. © 2003 Wiley‐Liss, Inc.
What it takes to become an effector T cell: The process, the cells involved, and the mechanisms
Authors: Santana M.A. , Rosenstein Y. 
Published: April 2003

AbstractWhen activated, CD4+ T cells differentiate into two major sub‐populations differing in their profiles of secreted cytokines. Type One, or TH1, cells secrete IL‐2, IFNγ, and TNFβ and mediate a cellular immune response. Type Two, or TH2, cells secrete IL‐4, IL‐5, IL‐6, IL‐10, and IL‐13 and potentiate a humoral response. The nature of any specific immune response depends on the interaction of antigen‐presenting cells and T cells. The role of antigen‐presenting cells is to respond to the nature of the immune challenge and signal differentiation of CD4+ T cells. A number of factors are involved in the effector phenotype of T cells—nature and affinity of antigen, co‐receptors signals, and cytokine environment. T‐cell differentiation is a complex process comprising four defined developmental stages: activation of particular cytokine genes, commitment of the cells, silencing of the opposing cytokine genes, and stabilization of the phenotype. In each of these stages, the cells respond to the products of many signaling cascades from many membrane‐bound receptors. The stages in development are mediated by different molecular mechanisms, involving control of gene expression and chromatin remodeling. This review centers on the factors, cellular interactions, and molecular mechanisms involved in the maturation of naïve CD4+ T lymphocytes into fully effector cells. © 2003 Wiley‐Liss, Inc.
Contribution of functional voltage‐gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: II. Secretory membrane activity
Authors: Mycielska M.E. , Fraser S.P. , Szatkowski M. , Djamgoz M.B.A. 
Published: April 2003

AbstractThe secretory membrane activities of two rat prostate cancer cell lines of markedly different metastatic potential, and corresponding electrophysiological characteristics, were studied in a comparative approach. In particular, voltage‐gated Na+ channels (VGSCs) were expressed in the strongly metastatic MAT‐LyLu but not in the closely related, but weakly metastatic, AT‐2 cells. Uptake and release of the non‐cytotoxic marker horseradish peroxidase (HRP) were used as indices of general endocytotic and exocytotic membrane activity, respectively. The amount of tracer present in a given experimental condition was quantified by light microscopic digital imaging. The uptake of HRP was an active process, abolished completely by incubating the cells at low temperature (5°C) and suppressed by disrupting the cytoskeleton. Interestingly, the extent of HRP uptake into the strongly metastatic MAT‐LyLu cells was almost twice that into the weakly metastatic AT‐2 cells. Vesicular uptake of HRP occurred in a fast followed by a slow phase; these appeared to correspond to cytoplasmic and perinuclear pools, respectively. Importantly, the overall quantitative difference in the uptake disappeared in the presence of 1 μM tetrodotoxin which significantly reduced the uptake of HRP into the MAT‐LyLu cells. There was no effect on the AT‐2 cells, consistent with functional VGSC expression occurring selectively in the former. A similar effect was observed in Na+‐free medium. The uptake was partially dependent upon extracellular Ca2+ but was not affected by raising the extracellular K+ concentration. We suggest that functional VGSC expression could potentiate prostate cancer cells' metastatic ability by enhancing their secretory membrane activity. © 2003 Wiley‐Liss, Inc.
Heme oxygenase‐1 in growth control and its clinical application to vascular disease
Authors: Durante William 
Published: April 2003

AbstractHeme oxygenase‐1 (HO‐1) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO‐1 originally centered on its heme‐degrading function, recent findings indicate that HO‐1 exerts other biologically important actions. Emerging evidence suggests that HO‐1 plays a critical role in growth regulation. Deletion of the HO‐1 gene or inhibition of HO‐1 activity results in growth retardation and impaired fetal development, whereas HO‐1 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO‐1 are not well established, HO‐1 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO‐1 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO‐1 are highly variable and may reflect a role for HO‐1 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO‐1 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO‐1 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO‐1 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders. © 2003 Wiley‐Liss, Inc.
MHC class I antigens, immune surveillance, and tumor immune escape
Authors: Garcia‐Lora Angel , Algarra Ignacio , Garrido Federico 
Published: April 2003

AbstractOncogenic transformation in human and experimental animals is not necessarily followed by the appearance of a tumor mass. The immune system of the host can recognize tumor antigens by the presentation of small antigenic peptides to the receptor of cytotoxic T‐lymphocytes (CTLs) and reject the nascent tumor. However, cancer cells can sometimes escape these specific T‐cell immune responses in the course of somatic (genetic and phenotypic) clonal evolution. Among the tumor immune escape mechanisms described to date, the alterations in the expression of major histocompatibility complex (MHC) molecules play a crucial step in tumor development due to the role of MHC antigens in antigen presentation to T‐lymphocytes and the regulation of natural killer cell (NK) cell function. In this work, we have (1) updated information on the mechanisms that allow CTLs to recognize tumor antigens after antigen processing by transformed cells, (2) described the altered MHC class I phenotypes that are commonly found in human tumors, (3) summarized the molecular mechanisms responsible for MHC class I alteration in human tumors, (4) provided evidence that these altered human leukocyte antigens (HLA) class I phenotypes are detectable as result of a T‐cell immunoselection of HLA class I‐deficient variants by an immunecompetent host, and (5) presented data indicating the MHC class I phenotype and the immunogenicity of experimental metastatic tumors change drastically when tumors develop in immunodeficient mice. © 2003 Wiley‐Liss, Inc.
Contribution of functional voltage‐gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. lateral motility
Authors: Fraser S.P. , Salvador V. , Manning E.A. , Mizal J. , Altun S. , Raza M. , Berridge R.J. , Djamgoz M.B.A. 
Published: April 2003

AbstractPrevious work suggested that functional voltage‐gated Na+ channels (VGSCs) are expressed specifically in strongly metastatic cells of rat and human prostate cancer (PCa), thereby raising the possibility that VGSC activity could be involved in cellular behavior(s) related to the metastatic cascade. In the present study, the possible role of VGSCs in the lateral motility of rat PCa cells was investigated in vitro by testing the effect of modulators that either block or enhance VGSC activity. Two rat PCa cell lines of markedly different metastatic ability were used in a comparative approach: the strongly metastatic MAT‐LyLu and the weakly metastatic AT‐2 cell line, only the former being known to express functional VGSCs. Using both electrophysiological recording and a motility assay, the effects of two VGSC blockers (tetrodotoxin and phenytoin) and four potential openers (veratridine, aconitine, ATX II, and brevetoxin) were monitored on (a) Na+ channel activity and (b) cell motility over 48 h. Tetrodotoxin (at 1 μM) and phenytoin (at 50 μM) both decreased the motility index of the MAT‐LyLu cell line by 47 and 11%, respectively. Veratridine (at 20 μM) and brevetoxin (at 10 nM) had no effect on the motility of either cell line, whilst aconitine (at 100 μM) and ATX II (at 25 pM) significantly increased the motility of the MAT‐LyLu cell line by 15 and 9%, respectively. Importantly, at the concentrations used, none of these drugs had effects on the proliferation or viability of either cell line. The results, taken together, would suggest strongly that functional VGSC expression enhances cellular motility of PCa cells. The relevance of these findings to the metastatic process in PCa is discussed. © 2003 Wiley‐Liss, Inc.
Synchronized prostate cancer cells for studying androgen regulated events in cell cycle progression from G1 into S phase
Authors: Cifuentes Eugenia , Croxen Richard , Menon Mani , Barrack Evelyn R. , Reddy G. Prem‐Veer 
Published: April 2003

AbstractAndrogen‐ablation is a most commonly prescribed treatment for metastatic prostate cancer but it is not curative. Development of new strategies for treatment of prostate cancer is limited partly by a lack of full understanding of the mechanism by which androgen regulates prostate cancer cell proliferation. This is due, mainly, to the limitations in currently available experimental models to distinguish androgen/androgen receptor (AR)‐induced events specific to proliferation from those that are required for cell viability. We have, therefore, developed an experimental model system in which both androgen‐sensitive (LNCaP) and androgen‐independent (DU145) prostate cancer cells can be reversibly blocked in G0/G1 phase of cell cycle by isoleucine deprivation without affecting their viability. Pulse‐labeling studies with 3H‐thymidine indicated that isoleucine‐deprivation caused LNCaP and DU145 cells to arrest at a point in G1 phase which is 12–15 and 6–8 h, respectively, before the start of S phase and that their progression into S phase was dependent on serum factors. Furthermore, LNCaP, but not DU145, cells required AR activity for progression from G1 into S phase. Western blot analysis of the cell extracts prepared at regular intervals following release from isoleucine‐block revealed remarkable differences in the expression of cyclin E, p21Cip1, p27Kip1, and Rb at the protein level between LNCaP and DU145 cells during progression from G1 into S phase. However, in both cell types Cdk‐2 activity associated with cyclin E and cyclin A showed an increase only when the cells transited from G1 into S phase. These observations were further corroborated by studies using exponentially growing cells that were enriched in specific phases of the cell cycle by centrifugal elutriation. These studies demonstrate usefulness of the isoleucine‐deprivation method for synchronization of androgen‐sensitive and androgen‐independent prostate cancer cells, and for examining the role of androgen and AR in progression of androgen‐sensitive prostate cancer cells from G1 into S phase. © 2003 Wiley‐Liss, Inc.
Über die wirkungsart von polymerisationsinhibitoren1
Authors: Schulz Von G. V. 
Published: April 2003

AbstractEine größere Anzahl von Stoffen wird auf ihre polymerisationshemmende Wirkung hin untersucht, indem ihr Einfluß auf die Geschwindigkeit der Polymerisation und den Polymerisationsgrad des entstehenden Produktes bestimmt wird. Die Messungen erlauben es, die Inhibitoren in 4 Klassen einzuteilen, je nachdem welchen Teilvorgang der Polymerisation sie beeinflussen. Gemeinsam mit Professor G. Wittig wird die Frage untersucht, ob Antioxydantien immer als Polymerisationsinhibitoren wirken. Es zeigt sich, daß alle untersuchten Polymerisationsinhibitoren auch die Autoxydation hemmen, daß aber viele Antioxydantien auf die Polymerisation keinen Einfluß haben.
Elektronenmikroskopische untersuchungen über submikroskopische fibrillen aus kunstfasern
Authors: Husemann Von E. , Carnap Mitarbeit von A. 
Published: April 2003

AbstractDurch elektronenmikroskopische Untersuchungen wird der Einfluß des Polyineri‐salionsgrades und der Orientierutg der Cellulosemoleküle auf die fibriänre Aufspaltung von Kunstfasern nach nasser Mahlung in der Kugelmühle sowie hydrolytischem Abbau geprüft. Dabei wird festgestellt, daß die Erhühung des Polymerisationsgrades allein ohne Einfluß auf die Art der Aufspaltung ist. Dagegen ruft eine Verbesserung der Orientieruüg der Makrornoleküle durch Verstrecküng im Fällungsbad die Bildung feiner glaeer Fibrillen hervor, wie man sie bisher nur bei netiven Fasern kannte. Eine nachträgliche Verslrcckung fertiger Fasern bewirkt nur eine Orientierung im äußeren Mantel und führt nicht zu ciner Fihrillenbildung. Eine vollständige Nachahmung der nativen Struktur ist jedoch auch durch diese Melhode nicht möglich; denn nach hydrolytischem Ahbau kommt es nicht zur Bildung von Fibrillmahschnitten, die bei gewachsenen Fasern als typische Strukturelemente gefunden wurden, da bei der Ausfällung die Lockerstellen der Cellulosemoleküle nicht in gleichen Ebenen liegen, also kein „Langperiodengitler”︁ entstehl.