Janusz Matuszyk
Research interests
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InterestsCancer Biology, Cell Culture, PCR
Publications
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[The mechanism of phospholipase Cγ1 activation].
Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:470-7.
Phospholipase C is an enzyme which catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) into second messengers inositol-1,4,5-triphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG). These messengers then promote the activation of protein kinase C and release of Ca(2+) from i... [more] Phospholipase C is an enzyme which catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) into second messengers inositol-1,4,5-triphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG). These messengers then promote the activation of protein kinase C and release of Ca(2+) from intracellular stores, initiating numerous cellular events including proliferation, differentiation, signal transduction, endocytosis, cytoskeletal reorganization or activation of ion channels. There have been identified 14 isozymes of PLC among which PLCγ1 and PLCγ2 are of particular interest. PLCγ contains catalytic region XY and a few regulatory domains: PH, EF and C2. The most unique features of these two enzymes are the Src homology domains (SH2, SH3) and split PH domain within the catalytic barrel. PLCγ1 and PLCγ2 have an identical domain structure, but they differ in their function and occurrence. Phospholipase Cγ1 is expressed ubiquitously, especially in the brain, thymus and lungs. PLCγ1 can be activated by receptor tyrosine kinases (i.e.: PDGFR, EGFR, FGFR, Trk), as well as non-receptor protein kinases (Src, Syk, Tec) or phosphatidic acid, tau protein and its analogue. The molecular mechanism of PLCγ1 activation includes membrane recruitment, phosphorylation, rearrangements and activation in the presence of growth factors. In reference to PLCγ1 regulation, a number of positive and negative modulators have been considered. The most important positive modulator is phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P(2)). Protein kinase A and C, tyrosine phosphatases (SHP-1, PTP-1B) and Cbl, Grb2, Jak2/PTP-1B complex proteins have been described as negative regulators of PLCγ1 activation.
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[The roles of orphan nuclear receptors in T-lymphocyte development in the thymus]
Postȩpy higieny i medycyny doświadczalnej (Online). 01/2009; 63:522-36.
T-lymphocyte development in the thymus proceeds through successive steps of differentiation,selection and expansion of thymocytes. Multiple signaling proteins and transcription factors play important roles in mediating the response to signals delivered through the pre-T-cell receptor (pre-TCR) and T... [more] T-lymphocyte development in the thymus proceeds through successive steps of differentiation,selection and expansion of thymocytes. Multiple signaling proteins and transcription factors play important roles in mediating the response to signals delivered through the pre-T-cell receptor (pre-TCR) and T-cell receptor (TCR) at two checkpoints during T-cell development. The orphan nuclear receptors RORg and Nur77 are involved in the differentiation and selection processes that are induced following activation of the pre-TCR and TCR, respectively, and they exert opposite effects on the survival of thymocytes. RORg activates the gene encoding the antiapoptotic protein Bcl-X(L) and is required for the survival of CD4+CD8+ thymocytes, while Nur77 is involved in the apoptosis of CD4+CD8+ thymocytes bearing TCRs with a high affinity for self antigens presented in the thymus.
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3.54Impact points
Inducibility of doxycycline-regulated gene in neural and neuroendocrine cells strongly depends on the appropriate choice of a tetracycline-responsive promoter.
Neurochemistry international. 02/2008; 52(1-2):221-9.
Elucidation of the mechanisms underlying specific receptor activation of neural and neuroendocrine cells will require the establishment of cellular systems that permit the regulation of the expression of the protein of interest. In a tetracycline (Tet)-regulated system, the gene encoding the protein... [more] Elucidation of the mechanisms underlying specific receptor activation of neural and neuroendocrine cells will require the establishment of cellular systems that permit the regulation of the expression of the protein of interest. In a tetracycline (Tet)-regulated system, the gene encoding the protein of interest is under the control of a Tet promoter and its transcription is activated in the presence of doxycycline (Dox) by the Tet transactivator rtTA. Acceptable inducibility of the gene's expression requires a high level of its expression in the presence of Dox and a minimal basal expression in the absence of Dox. Two Tet promoters are compared here, the original PhCMV*-1 and the second-generation Ptight, with respect to the inducibility of the gene of interest in neuroendocrine and neural cells genetically engineered to express rtTA, namely PC12-Tet-On cells and MB-G-18 cells (mouse brain-derived cells with the phenotype of neuron-restricted precursors). This study demonstrates that the use of Ptight provided a much higher Dox-induced maximal expression in both cell lines, while the basal activities of the two Tet promoters were at similar levels. The additional use of the Tet-controlled silencer (tTS) caused almost complete abrogation of the leakiness of the Ptight promoter and an increase in the inducibility of the regulated gene, but the maximal levels of gene expression driven in the presence of Dox were also markedly reduced.
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3.54Impact points
Transactivation activity of Nur77 discriminates between Ca2+ and cAMP signals.
Neurochemistry international. 04/2005; 46(4):305-12.
The orphan nuclear receptors Nur77 and Nurr1 are the members of the Nur77 family of transcription factors. We demonstrate that transcription of the Nur77 family genes was upregulated in PC12 cells following incubation with Ca2+ ionophore as well as cyclic AMP (cAMP) analog. On the other hand, cAMP a... [more] The orphan nuclear receptors Nur77 and Nurr1 are the members of the Nur77 family of transcription factors. We demonstrate that transcription of the Nur77 family genes was upregulated in PC12 cells following incubation with Ca2+ ionophore as well as cyclic AMP (cAMP) analog. On the other hand, cAMP analog induced strong increase, while Ca2+ ionophore induced weak increase in the transactivation activity of Nur77. We found that Nur77 and Nurr1 proteins were expressed in the nucleus following stimulation with cAMP analog but not after stimulation with Ca2+ ionophore. However, expression of Nur77 protein was increased in the cytoplasm of cells treated with Ca2+ ionophore. In conclusion, our results suggest that cAMP-induced and Ca2+-induced processes may differentially regulate activity of Nur77 at the level of translocation of Nur77 protein from the cytoplasm into the nucleus.
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2.55Impact points
Early neuronal progenitor cell line expressing solely non-catalytic isoform of TrkC.
Biochemical and biophysical research communications. 10/2003; 309(1):91-5.
TrkC is a receptor for neurotrophin-3 that regulates development of neuronal precursors. Transduction of signals into receptor-dependent signaling pathways is mainly due to the activation of the intrinsic tyrosine kinase of the TrkC receptor. Alternative splicing of the trkC transcripts generates ca... [more] TrkC is a receptor for neurotrophin-3 that regulates development of neuronal precursors. Transduction of signals into receptor-dependent signaling pathways is mainly due to the activation of the intrinsic tyrosine kinase of the TrkC receptor. Alternative splicing of the trkC transcripts generates catalytic and non-catalytic isoforms. The non-catalytic isoform, denoted as TrkC-NC2, contains unique sequence, instead of deleted entire kinase domain. Here, we report that neural cell line MB-G, derived from brain of embryos of transgenic tsA58-SV40 mice, contains mRNA encoding TrkC-NC2 without concomitant expression of mRNA for catalytic TrkC molecule.
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2.55Impact points
Nurr1 affects pRL-TK but not phRG-B internal control plasmid in genetic reporter system.
Biochemical and biophysical research communications. 07/2002; 294(5):1036-9.
In transcription assays, Renilla luciferase-expressing plasmids (more specifically pRL-TK) are commonly used as an internal control of transfection efficiency. Normalization of the experimental reporter gene transcription to the internal control reporter gene transcription minimizes variability of o... [more] In transcription assays, Renilla luciferase-expressing plasmids (more specifically pRL-TK) are commonly used as an internal control of transfection efficiency. Normalization of the experimental reporter gene transcription to the internal control reporter gene transcription minimizes variability of obtained results caused by differences in transfection efficiency between different samples of transfected cells. It is obvious that co-transfection with other plasmids or applied treatments should not affect the activity of the control reporter. Here we report that expression of the control Renilla luciferase encoded by pRL-TK plasmid was enhanced by co-transfection with vectors expressing orphan nuclear receptors Nur77 family (Nur77, Nurr1, Nor-1), leading to misinterpretation of the assay results. Further, we show that for Nurr1, phRG-B (a promoterless reporter plasmid containing synthetic Renilla luciferase gene) is a better control reporter vector than HSV-TK containing vectors. Finally, we noted the lack of effect of Nurr1 protein on the Fas Ligand promoter-driven transcription.
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2.21Impact points
HA1004, an inhibitor of serine/threonine protein kinases, restores the sensitivity of thymic lymphomas to Ca2+-mediated apoptosis through a protein kinase A-independent mechanism.
International immunopharmacology. 04/2002; 2(4):435-42.
Our previous reports showed that thymic lymphomas arising in TCR transgenic mice are resistant to Ca2+-mediated apoptosis. Here we show that induction of apoptosis in thymic lymphomas involves a process that is cAMP-mediated and which depends on the activation of protein kinase A (PKA) despite the l... [more] Our previous reports showed that thymic lymphomas arising in TCR transgenic mice are resistant to Ca2+-mediated apoptosis. Here we show that induction of apoptosis in thymic lymphomas involves a process that is cAMP-mediated and which depends on the activation of protein kinase A (PKA) despite the lower level of PKA type I in these lymphomas compared to thymocytes. Further, we show that treatment of the lymphomas with HA1004, a serine/threonine protein kinase inhibitor, restores their susceptibility to ionomycin-induced apoptosis. Results indicate that HA1004-induced restoration of sensitivity to ionomycin proceeds through a PKA-independent mechanism. Moreover, activation of PKA instead of its inhibition induces apoptosis of lymphoma cells.
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1.99Impact points
Changes in glucocorticoid-induced apoptosis and in expression of Bcl-2 protein during long-term culture of thymic lymphoma.
Archivum immunologiae et therapiae experimentalis. 02/2000; 48(1):43-6.
Lymphomagenesis is a multistep process progressively freeing transformed thymocytes from external regulatory signals, i.e. thymic developmental program controlling growth, differentiation or apoptosis. Here we report that cells of thymic lymphoma overexpressing Ras/Raf proteins, initially resistant ... [more] Lymphomagenesis is a multistep process progressively freeing transformed thymocytes from external regulatory signals, i.e. thymic developmental program controlling growth, differentiation or apoptosis. Here we report that cells of thymic lymphoma overexpressing Ras/Raf proteins, initially resistant to TCR-dependent apoptosis but sensitive to dexamethasone- and etoposide-induced cell death, became insensitive to dexamethasone after long-time culture. That transition correlated with a strong increase in the expression of the anti-apoptotic Bcl-2 protein. Interestingly, lymphoma cells were still sensitive to p53-mediated apoptosis induced by etoposide. It suggests that the anti-apoptotic activity of Bcl-2 is correlated with a resistance to glucocorticoid-induced apoptosis but not to p53-mediated apoptosis. The sequence of mutations in the process of lymphomagenesis seems to be composed of at least 3 main hits which equip the cells with independence from external mitogenic signals (activation of Ras/Raf), resistance to inducers of apoptosis (activation of Bcl-2) and generation of cellular heterogeneity (deletion of p53) important in tumor progression.
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2.36Impact points
Overexpression of Ras, Raf and L-myc but not Bcl-2 family proteins is linked with resistance to TCR-mediated apoptosis and tumorigenesis in thymic lymphomas from TCR transgenic mice.
Leukemia research. 02/2000; 24(1):33-8.
Mice with transgenic TCR anti H-Y/Db develop spontaneous thymic tumors with a high frequency (up to 50%). Oncogenicity of TCR transgenes could depend on the deregulated expression of oncoproteins engaged in transduction pathways leading to proliferation or apoptosis. In agreement with this possibili... [more] Mice with transgenic TCR anti H-Y/Db develop spontaneous thymic tumors with a high frequency (up to 50%). Oncogenicity of TCR transgenes could depend on the deregulated expression of oncoproteins engaged in transduction pathways leading to proliferation or apoptosis. In agreement with this possibility we have found that cells of thymic lymphomas from TCR transgenic mice were largely resistant to TCR-dependent Ca++-mediated apoptosis but not to TCR-independent, p53-mediated (etoposide) apoptosis. Here we show raised expression of Bcl-2 protein in some but not in all thymic lymphoma cell lines. It suggests that the antiapoptotic function of Bcl-2 is not necessary for the process of tumorigenesis and the resistance of these lymphomas to Ca++-mediated apoptosis. On the other hand we show that all thymic lymphomas overexpressed Ras/Raf and L-myc proteins. Stimulation of the Ras/Raf pathway was reported to be required to maintain cell viability by preventing programmed cell death in thymic tumors derived from lck transgenic mice. Similarly, in TCR transgenic lymphomas overexpression of Ras, Raf and L-myc but not Bcl-2 family proteins may be responsible for the resistance of these lymphomas to TCR-mediated apoptosis but not affect p53-mediated apoptosis.
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[The role of vav protein in TCR-mediated signaling with MHC/peptide complexes leading to positive or negative selection of thymocytes]
Postȩpy higieny i medycyny doświadczalnej. 02/1999; 53(4):531-43.
On the basis of recent reports we discuss the role of Vav in TCR-dependent signaling pathways. The Vav protein is GDP/GTP exchange factor for Rac, which initiates transduction of signals in JNK pathway. Upon stimulation of TCR by antigenic peptides, Vav associates with Zap-70 in TCR/CD3 signaling co... [more] On the basis of recent reports we discuss the role of Vav in TCR-dependent signaling pathways. The Vav protein is GDP/GTP exchange factor for Rac, which initiates transduction of signals in JNK pathway. Upon stimulation of TCR by antigenic peptides, Vav associates with Zap-70 in TCR/CD3 signaling complex and becomes phosphorylated on Tyr-174 by tyrosine kinase Lck. The function of Vav is modulated by substrates and products of PI3-kinase activated by interaction of CD28 on thymocytes with B7 on antigen presenting cells. The PI3-kinase substrates inhibit activation of Vav, while the products enhance phosphorylation and activation of Vav by Lck. It seems that Vav functions in key point of TCR-mediated signaling pathway, which is regulated by costimulatory molecule (CD28) necessary for negative selection. The Vav-mediated integration of signals results in positive or negative selection of thymocytes.
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2.55Impact points
Thymic lymphomas are resistant to Nur77-mediated apoptosis.
Biochemical and biophysical research communications. 09/1998; 249(1):279-82.
We reported previously that thymic lymphomas from mice expressing transgenic TCR autoreactive against male (HY) antigen were resistant to anti-CD3 antibody-mediated induction of apoptosis although they were responding to TCR triggering. To test whether thymic lymphomas were specifically resistant to... [more] We reported previously that thymic lymphomas from mice expressing transgenic TCR autoreactive against male (HY) antigen were resistant to anti-CD3 antibody-mediated induction of apoptosis although they were responding to TCR triggering. To test whether thymic lymphomas were specifically resistant to TCR-dependent Ca(++)-mediated induction of apoptosis, we have measured apoptosis of cells treated with Ca(++)-dependent (ionomycin, A23187) and Ca(++)-independent (etoposide, dexamethasone) inducers of apoptosis. Here we show that, unlike thymocytes, all thymic lymphomas were resistant to Ca(++)-dependent but not to Ca(++)-independent induction of apoptosis. These results excluded a general defect of apoptosis in lymphoma cells and suggested a specific inhibition of the calcium-mediated (TCR-dependent) pathway of apoptosis in lymphomas. Interestingly however, nuclear expression of a specific mediator of TCR-dependent apoptosis Nur77 was induced in ionomycin-resistant lymphomas indicating that, unlike normal thymocytes, thymic lymphomas are resistant to Nur77-mediated apoptosis.
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[Signaling pathways and their role in maturation and function of T lymphocytes]
Postȩpy higieny i medycyny doświadczalnej. 02/1997; 51(4):351-65.
Signals delivered through the beta/gp33 (pre-TCR) and T-cell receptor alpha beta control proliferation and differentiation of thymocytes at two distinct control points of T cell maturation. Interaction between T-cell receptor (TCR) and peptide/MHC complex induce signaling pathways leading to activat... [more] Signals delivered through the beta/gp33 (pre-TCR) and T-cell receptor alpha beta control proliferation and differentiation of thymocytes at two distinct control points of T cell maturation. Interaction between T-cell receptor (TCR) and peptide/MHC complex induce signaling pathways leading to activation of T cell. Signal transduction involves CD3 zeta phosphorylation by Lck tyrosine kinase and activation of ZAP-70 which regulates signaling pathways through PKC, Ca++ and Ras/Raf kinase cascade. Appropriate response of cell is preceded by integration of different signals in the nucleus.
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1.99Impact points
Loss of T cell receptor diminished tumorigenicity of thymocyte-derived lymphoma cells in the T cell receptor transgenic mice.
Archivum immunologiae et therapiae experimentalis. 01/1997; 45(4):307-13.
Mice with transgenic T cell receptor (TCR) recognizing H-Y male antigen developed spontaneous lymphomas originated from immature thymocytes, with the surface expression of transgenic TCR and CD4/CD8 co-receptors. During in vitro long-term culture (3 months) some lymphoma cell lines lost the surface ... [more] Mice with transgenic T cell receptor (TCR) recognizing H-Y male antigen developed spontaneous lymphomas originated from immature thymocytes, with the surface expression of transgenic TCR and CD4/CD8 co-receptors. During in vitro long-term culture (3 months) some lymphoma cell lines lost the surface expression of TCR and co-receptors. Interestingly, the proteins of transgenic receptor were expressed intracellularly but TCR was not detectable on the surface of the in vitro selected subline in contrast to TCR-positive parental cells maintained in vivo. TCR-negative subline has been found to be slowly growing in vivo (i.p. injection) and less tumorigenic (s.c. injection) than parental TCR positive lymphoma. It seems that the in vivo interactions of lymphoma cells with microenvironment preserve their TCR expression and endow with growth advantage, while the selected in vitro TCR-negative cells lose the tumorigenic potential.
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3.40Impact points
Role of thymic selection in the development of thymic lymphomas in TCR transgenic mice.
International immunology. 01/1997; 9(1):127-38.
To investigate the role of antigen receptor-mediated interactions in lymphomagenesis we have analyzed the influence of alpha beta TCR-mediated selection on the development of spontaneous thymic lymphomas, which appear with a high (up to 50%) frequency in mice expressing a transgenic TCR specific for... [more] To investigate the role of antigen receptor-mediated interactions in lymphomagenesis we have analyzed the influence of alpha beta TCR-mediated selection on the development of spontaneous thymic lymphomas, which appear with a high (up to 50%) frequency in mice expressing a transgenic TCR specific for the male antigen (HY) in the context of H-2Db molecules. To this end we compared the kinetics and the incidence of thymic lymphomas developing in females and males with selecting (H-2b) and non-selecting (H-2k) MHC molecules. The kinetics of development of thymic lymphomas was similar in positively selecting (H-2b females) and non-selecting (H-2k females and males) environments but significantly slower (P < 0.01) in the negatively selecting environment (H-2b male). Injection of lymphoma cells derived from a H-2b female into the thymus of a H-2b male resulted in strong, antigen-specific inhibition of growth, indicating that the slower kinetics of lymphomagenesis in H-2b males could be due, at least partially, to the sensitivity of oncogenically transformed thymocytes to TCR-mediated negative selection. Phenotypic and functional analysis of lymphoma cells indicated that they originated from the stage of pre-TCR-dependent transition of immature CD4-CD8- to CD4+ CD8+ thymocytes, which in H-2b females and males developed into tumors under different environmental pressures. These results failed to provide convincing evidence for the role of positive selection but provided a strong indication that self antigen-induced negative selection, in addition to its well established role in self tolerance, can occasionally act as a tumor surveillance mechanism by eliminating or suppressing growth of thymocytes undergoing oncogenic transformation.
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1.99Impact points
Unexpected reaction of anti-H-2d serum with thymic lymphoma cells derived from transgenic B6-H-2b TCR anti-HY/Db mice.
Archivum immunologiae et therapiae experimentalis. 02/1996; 44(2-3):103-7.
Transgenic mice with alpha beta TCR specific for male antigen (HY) in the context of H-2Db MHC class I were prepared by introduction of transgens into (C57BL/6J x DBA/2J)F1 hybrid mice (H-2b/d), where only H-2b is selective for maturating thymocytes. Founder transgenic mouse was backcrossed to H-2b ... [more] Transgenic mice with alpha beta TCR specific for male antigen (HY) in the context of H-2Db MHC class I were prepared by introduction of transgens into (C57BL/6J x DBA/2J)F1 hybrid mice (H-2b/d), where only H-2b is selective for maturating thymocytes. Founder transgenic mouse was backcrossed to H-2b MHC background. Serological typing of H-2 antigens revealed that transgenic mice do not express H-2d antigens. Unexpectedly, cells of thymic lymphomas, spontaneously developed in about 45% of old B6 (H-2b) transgenic mice and peripheral blood lymphocytes of about 40% of transgenic mice, reacted with anti-H-2d serum (strain 129 mice (H-2b) immunized with thymocytes and splenocytes of BALB/c mice) but not with monoclonal antibodies against H-2d MHC class I antigens. Anti-H-2d serum has been shown to react with thymocytes but not peripheral blood lymphocytes from non-transgenic H-2b mice. The lymphocytes of transgenic mice reacting with anti-H-2d serum could represent disseminating preneoplastic or neoplastic cells expressing antigen encoded outside MHC region and present on the cell surface of immature thymocytes but not lymphocytes in healthy mice.
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[Use of anti-H-Y/Db transgenic mice in studies on T-lymphocyte development and mechanisms of leukemogenesis]
Postȩpy higieny i medycyny doświadczalnej. 02/1995; 49(1):61-5.
During the development of T cells in the thymus, the alpha beta T-cell receptor (TCR) mediated interactions of immature CD4+ CD8+ cells with thymic major histocompatibility complex (MHC) molecules in the absence of specific antigens are required for their survival and further maturation (positive se... [more] During the development of T cells in the thymus, the alpha beta T-cell receptor (TCR) mediated interactions of immature CD4+ CD8+ cells with thymic major histocompatibility complex (MHC) molecules in the absence of specific antigens are required for their survival and further maturation (positive selection) whereas interactions with MHC molecules presenting specific antigens result in their death by apoptosis (negative selection). Preliminary results suggest association of antigenic stimulation via TCR with leukemogenesis of TCR transgenic mice. TCR transgenic mice monitored over a period of 2 years revealed spontaneous leukemia development in mice of both sexes by the age of 8-12 months, with the surface expression of transgene and markers of T cell development pathway.
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3.20Impact points
Mutation and altered expression of p53 genes in experimental rat bladder tumor cells.
Molecular carcinogenesis. 03/1994; 9(2):95-104.
p53 genes were analyzed for mutations and expression in a series of 24 tumors or hyperplastic lesions of the urinary bladder induced in F344 rats by carcinogen treatment. Of these, 18 were analyzed as short-term urothelial cultures. Polymerase chain reaction-single-strand conformation polymorphism a... [more] p53 genes were analyzed for mutations and expression in a series of 24 tumors or hyperplastic lesions of the urinary bladder induced in F344 rats by carcinogen treatment. Of these, 18 were analyzed as short-term urothelial cultures. Polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing were used to detect alterations in p53 genes or cDNAs, and the relative amounts of p53 protein per cell were estimated by immunohistochemical staining. Missense substitutions were found in the exon 5-9 region of two of five cell cultures analyzed from lesions induced by the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. One of these was a papillary nodular hyperplasia, indicating that p53 mutations can be present in low- as well as high-stage/grade bladder lesions. p53 mutations were not found in the exon 5-9 region in cells of any of eight bladder lesions induced by N-[4-(5-nitro-2-furyl)-2- thiazoly]formamide (FANFT), including five transitional cell carcinomas (TCCs), or either of two TCCs induced by N-methylnitrosourea. Two of nine TCCs induced by the N-glucuronide of N-hydroxy-2-aminofluorene were found to have p53 mutations. One of these was evidently altered by three genetic events: a missense substitution in exon 8, a nonsense mutation in exon 6, and silencing of the "nonsense" allele (i.e., only the p53 missense mutation was detected). Immunohistochemical analysis with monoclonal antibody PAb240 (which preferentially binds to mutant p53 protein) detected p53 antigen only in those samples in which missense p53 mutations were found. With monoclonal antibody PAb421 (which detects mutant and wild-type p53), p53 antigen was also detected in cells from F542, a bladder tumor induced by FANFT in which no p53 mutations were found. Northern blot hybridization analysis showed that p53 transcripts were elevated twofold to threefold in several cases, including F542, suggesting that constitutive overexpression of wild-type p53 may occur in some bladder neoplasias. These data support the view that p53 may be involved in multiple rate-limiting steps in neoplastic transformation and may be a continuing target during bladder carcinogenesis. The data also contribute to evidence that certain chemical carcinogens may directly alter p53 genes during tumorigenesis.
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[Diversity of signal transduction pathways which induce apoptosis of thymocytes. Role of bcl-2, pim-1, c-myc and p53 genes in selection processes of thymocytes]
Postȩpy higieny i medycyny doświadczalnej. 02/1994; 48(6):663-75.
There are independent signaling pathways which transmit apoptotic signals in thymocytes. c-Myc and p53 proteins participate in the apoptosis induction, whereas Bcl-2 and Pim-1 proteins inhibit complex apoptotic machinery.... [more] There are independent signaling pathways which transmit apoptotic signals in thymocytes. c-Myc and p53 proteins participate in the apoptosis induction, whereas Bcl-2 and Pim-1 proteins inhibit complex apoptotic machinery.
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1.99Impact points
Interleukin 3-dependent, asialo-GM1-positive cell line with natural cytotoxic but without natural killer cytotoxic activity.
Archivum immunologiae et therapiae experimentalis. 02/1994; 42(3):179-83.
IL-3-dependent cell line (designated as A-3) from adherent spleen cells was developed. The surface phenotype of A-3 cells was analysed by flow cytometry and determined as ASGM1+, FcR+, Ia+. There was no expression of T cell markers (Th1-CD3-CD4-CD8-), B cell marker (surface Ig) as well as macrophage... [more] IL-3-dependent cell line (designated as A-3) from adherent spleen cells was developed. The surface phenotype of A-3 cells was analysed by flow cytometry and determined as ASGM1+, FcR+, Ia+. There was no expression of T cell markers (Th1-CD3-CD4-CD8-), B cell marker (surface Ig) as well as macrophage marker Mac-1 antigen. Although A-3 cells expressed ASGM1, they are lacking NK cytotoxic activity in 4 h Cr release assay with YAC-1 targets. In contrast, A-3 cells are endowed with NC cytotoxic activity as shown in 18 h Cr release assay with WEHI-164 target cells.
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0.89Impact points
Antitumor activity evaluation of bromine-substituted analogues of ifosfamide. I. Stereodifferentiation of biological effects and selection of the most potent compounds.
Immunopharmacology and immunotoxicology. 02/1992; 14(4):883-911.
The series of 9 compounds, including 3 racemates and 6 enantiomers of bromine-substituted analogues of ifosfamide (bromo-, chlorobromo- and dibromofosfamides) have been evaluated for antitumor activity against L1210 leukemia, Lewis lung carcinoma and B16 melanoma in mice. Effective and curative dose... [more] The series of 9 compounds, including 3 racemates and 6 enantiomers of bromine-substituted analogues of ifosfamide (bromo-, chlorobromo- and dibromofosfamides) have been evaluated for antitumor activity against L1210 leukemia, Lewis lung carcinoma and B16 melanoma in mice. Effective and curative doses of tested compounds were estimated on the basis of computer-assisted elaboration of the dose-effect curves obtained from experimental data. Two oxazaphosphorine drugs, ifosfamide and its congener cyclophosphamide, were used as referentials. Elementary toxicity studies were conducted in parallel in healthy animals and lethal doses were determined. Selection of the most potent compounds was based on the comparison of their therapeutic indices, calculated from the ratio of lethal to effective doses. In effect four compounds which have been shown therapeutically more effective than both referential drugs, were selected for further evaluation in mice bearing advanced tumours. Stereodifferentiation of evaluated biologic effects favouring S(-) isomers was observed in all three groups of compounds. Preliminary observation was also made indicating significant lethality reduction after per os administration of selected agents, which was not paralleled by diminution of their antitumor effectivity.
Following (1)
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Leon Strzadala
Institute of Immunology and Experimental Therapy
Topics (9)
