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  1. Article ; Online: Poly(I:C) treatment influences the expression of calreticulin and profilin-1 in a human HNSCC cell line: a proteomic study.

    Matijević, Tanja / Pavelić, Jasminka

    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

    2012  Volume 33, Issue 4, Page(s) 1201–1208

    Abstract: Polyinosinic:polycytidylic acid (poly (I:C)) has been formerly known to be an interferon inducer but the mechanism of its action was not revealed until the discovery of Toll-like receptors (TLRs). TLRs are members of transmembrane proteins that recognize ...

    Abstract Polyinosinic:polycytidylic acid (poly (I:C)) has been formerly known to be an interferon inducer but the mechanism of its action was not revealed until the discovery of Toll-like receptors (TLRs). TLRs are members of transmembrane proteins that recognize conserved molecular motifs of viral and bacterial origin and initiate innate immune response. Recent studies have shown that they are also expressed on tumor cells, but their role in these cells is still not clear. TLR3 recognizes double-stranded RNA (poly (I:C)) and is primarily involved in the defense against viruses. TLR3 ligand binding initiates the activation of transcription factors NF-κB, IRF family members, and AP-1, which can induce wide cascading effect on the cell and consequently activate many cellular processes. Since little is known about TLR3 target genes, we have used the proteomic approach to widen the current knowledge. In this study, we have discovered 15 differentially expressed proteins, mostly connected with protein metabolic processes. Furthermore, we have confirmed by Western blot that calreticulin and profilin-1, proteins which have been shown previously to be involved in processes connected with tumor progression, are differentially expressed after poly(I:C) treatment. By using TLR3 small interfering RNA, we showed that calreticulin expression might be TLR3 dependent, unlike profilin-1.
    MeSH term(s) Blotting, Western ; Calreticulin/metabolism ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; Down-Regulation/drug effects ; Electrophoresis, Gel, Two-Dimensional ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/metabolism ; Head and Neck Neoplasms/pathology ; Humans ; Mass Spectrometry ; Poly I-C/pharmacology ; Profilins/metabolism ; Proteome/metabolism ; Proteomics/methods ; RNA Interference ; Toll-Like Receptor 3/genetics ; Toll-Like Receptor 3/metabolism ; Up-Regulation/drug effects
    Chemical Substances Calreticulin ; Profilins ; Proteome ; Toll-Like Receptor 3 ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 2012-03-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605825-5
    ISSN 1423-0380 ; 0289-5447 ; 1010-4283
    ISSN (online) 1423-0380
    ISSN 0289-5447 ; 1010-4283
    DOI 10.1007/s13277-012-0366-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The dual role of TLR3 in metastatic cell line.

    Matijevic, Tanja / Pavelic, Jasminka

    Clinical & experimental metastasis

    2011  Volume 28, Issue 7, Page(s) 701–712

    Abstract: Toll-like receptors (TLRs) are members of transmembrane proteins that recognize conserved molecular motifs of viral and bacterial origin and initiate innate immune response. As the role of TLRs in tumors cells is still not clear, our aim was to ... ...

    Abstract Toll-like receptors (TLRs) are members of transmembrane proteins that recognize conserved molecular motifs of viral and bacterial origin and initiate innate immune response. As the role of TLRs in tumors cells is still not clear, our aim was to investigate the role of TLR3 in primary tumor and metastatic cells (SW480, SW620, FaDu and Detroit 562). We have reported here on the dual role of TLR3 in pharynx metastatic cell line (Detroit 562); on one hand TLR3 activation drove cells to apoptosis while on the other its stimulation contributed to tumor progression by altering the expression of tumor promoting genes (PLAUR, RORB) and enhancing the cell migration potential. In addition, we have shown TLR3 signaling pathway is functional in another metastatic cancer cell line (SW620) suggesting TLR3 might be important in the process of tumor metastasis. Since TLR3 agonists have been used in tumor therapy with the aim to activate immune system, scientific contribution of this work is drawing attention to the importance of further work on this topic, especially pro-tumor effect of TLR3, in order to avoid possible side-effects.
    MeSH term(s) Apoptosis ; Cell Line, Tumor ; Cell Movement ; Colonic Neoplasms/genetics ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Metastasis/genetics ; Neoplasm Metastasis/pathology ; Pharyngeal Neoplasms/metabolism ; Pharyngeal Neoplasms/pathology ; Pharyngeal Neoplasms/secondary ; Signal Transduction ; Toll-Like Receptor 3/genetics ; Toll-Like Receptor 3/metabolism
    Chemical Substances Toll-Like Receptor 3
    Language English
    Publishing date 2011-07-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 604952-7
    ISSN 1573-7276 ; 0262-0898
    ISSN (online) 1573-7276
    ISSN 0262-0898
    DOI 10.1007/s10585-011-9402-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Antitumor activity from the combined application of poly(I:C) and chemotherapeutics in human metastatic pharyngeal cell lines.

    Matijević, Tanja / Kirinec, Gabriela / Pavelić, Jasminka

    Chemotherapy

    2011  Volume 57, Issue 6, Page(s) 460–467

    Abstract: Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy.! ...

    Abstract Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy.
    Methods: Human pharyngeal cancer cell lines were studied (FaDu and Detroit 562). Cytotoxicity assays and apoptosis assays (annexin V staining and caspase 3/7 activity measurements) were used to investigate the cytotoxic effects. By using TLR3 siRNA we confirmed that the observed effect is TLR3-dependent.
    Results: We found that the combined application of poly(I:C) and chemotherapeutics (cisPt, HU, 5-FU and MTX) has a stronger inhibitory effect on cell growth in tumor cells expressing functional TLR3 as compared with a single treatment. This is a result of TLR3-dependent apoptosis.
    Conclusion: Our study showed that a combined application of the two agents already being used in tumor therapy could lower the necessary dosage of chemotherapeutics, leading to fewer side effects.
    MeSH term(s) Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Humans ; Pharyngeal Neoplasms/drug therapy ; Pharyngeal Neoplasms/pathology ; Poly I-C/administration & dosage
    Chemical Substances Antineoplastic Agents ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 2011
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6708-8
    ISSN 1421-9794 ; 0009-3157
    ISSN (online) 1421-9794
    ISSN 0009-3157
    DOI 10.1159/000334122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Rett syndrome: from the gene to the disease.

    Matijevic, Tanja / Knezevic, Jelena / Slavica, Marko / Pavelic, Jasminka

    European neurology

    2009  Volume 61, Issue 1, Page(s) 3–10

    Abstract: Rett syndrome (RTT, MIM No. 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation. It is transmitted as an X-linked dominant trait, therefore almost exclusively affecting females. About 80% of RTT ... ...

    Abstract Rett syndrome (RTT, MIM No. 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation. It is transmitted as an X-linked dominant trait, therefore almost exclusively affecting females. About 80% of RTT cases are sporadic caused by mutations in the MECP2 gene located on Xq28. The gene codes for two isoforms of the methyl-CpG-binding protein (MeCP2, MeCP2B) which are involved in transcriptional silencing through DNA methylation. The gene has 4 exons. The fourth one is the largest. Almost all mutations in MECP2 occur de novo. Although mutations are dispersed throughout the gene, about 67% of all MECP2 mutations, caused by C>T transitions at 8 CpG dinucleotides, are located in the third and fourth exon. The most common mutation is R168X. So far, there is no clear evidence on genotype-phenotype correlations. There are also reports claiming that the same mutation can provoke different phenotypes. It was shown that MeCP2 can silence certain genes. One of them, brain-derived neurotrophic factor, is essential for neural plasticity, learning and memory. This discovery revealed the role of MeCP2 in the control of neuronal activity-dependent gene regulation and suggested that the pathology of RTT may result from deregulation of this process.
    MeSH term(s) Genotype ; Humans ; Methyl-CpG-Binding Protein 2/genetics ; Mutation ; Phenotype ; Rett Syndrome/genetics ; Rett Syndrome/pathology
    Chemical Substances MECP2 protein, human ; Methyl-CpG-Binding Protein 2
    Language English
    Publishing date 2009
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 209426-5
    ISSN 1421-9913 ; 0014-3022
    ISSN (online) 1421-9913
    ISSN 0014-3022
    DOI 10.1159/000165342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Biological & physiological aspects of action of insulin-like growth factor peptide family.

    Pavelić, Jasminka / Matijević, Tanja / Knezević, Jelena

    The Indian journal of medical research

    2007  Volume 125, Issue 4, Page(s) 511–522

    Abstract: The insulin-like growth factor (IGF) is a complex system of peptide hormones (insulin-like growth factors of type 1 and 2, IGF-1 and IGF-2), cell surface receptors (insulin receptor, IR; insulin-like growth factor receptors of type 1 and 2, IGF-R1, IGF- ... ...

    Abstract The insulin-like growth factor (IGF) is a complex system of peptide hormones (insulin-like growth factors of type 1 and 2, IGF-1 and IGF-2), cell surface receptors (insulin receptor, IR; insulin-like growth factor receptors of type 1 and 2, IGF-R1, IGF-R2) and circulating binding proteins (insulinlike growth factor binding proteins, IGF-BP 1-6). IGF-1 and -2 are mitogens that play a role in regulating cell proliferation, differentiation and apoptosis. Their effects are mediated through the IGF-R1 which initiates signaling cascades that result in regulation of a number of biological responses. IGF-R2, together with IGF-BPs is involved in binding, internalization and degradation of IGF-2. IGF proteins regulate cell proliferation in an interconnected action via autocrine, paracrine and endocrine regulatory mechanisms. Consequently, any perturbation in each level of the IGF signaling proteins has been shown to be implicated in development and progression of numerous cancer types. The most important single components in this processes are IGF ligands as well as IGF-R1 - when disturbed they act as oncogenes. It has been shown that: (i) high serum concentrations of IGF-1 and IGF-2 are associated with an increased risk of breast, prostate, colorectal and lung cancers; and (ii) IGF-R1 is commonly disturbed in many tumours (like gastric, lung, endometrial cancer) leading to a phenotype of anchorage-independent tumour growth. In contrast, IGF-R2 is considered to act as a tumour suppressor gene; it protects the cells from neoplastic impulses. Consistent with the IGFs autocrine/paracrine regulation of tumour growth, cancer treatment strategies interfering with IGF-R1 signaling have been developed, that may be useful in future diagnostic and therapeutic strategies.
    MeSH term(s) Animals ; Growth Hormone/metabolism ; Humans ; Insulin/genetics ; Insulin/metabolism ; Insulin-Like Growth Factor Binding Proteins/genetics ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Neoplasms/metabolism ; Receptors, Somatomedin/genetics ; Receptors, Somatomedin/metabolism ; Signal Transduction/physiology ; Somatomedins/genetics ; Somatomedins/metabolism
    Chemical Substances Insulin ; Insulin-Like Growth Factor Binding Proteins ; Receptors, Somatomedin ; Somatomedins ; Growth Hormone (9002-72-6)
    Language English
    Publishing date 2007-04
    Publishing country India
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 390883-5
    ISSN 0971-5916 ; 0019-5340
    ISSN 0971-5916 ; 0019-5340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

    Matijević, Tanja / Kirinec, Gabriela / Pavelić, Jasminka

    Chemotherapy

    2011  Volume 57, Issue 6, Page(s) 460–467

    Abstract: Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy. ... ...

    Institution Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
    Abstract Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy. Methods:Human pharyngeal cancer cell lines were studied (FaDu and Detroit 562). Cytotoxicity assays and apoptosis assays (annexin V staining and caspase 3/7 activity measurements) were used to investigate the cytotoxic effects. By using TLR3 siRNA we confirmed that the observed effect is TLR3-dependent. Results: We found that the combined application of poly(I:C) and chemotherapeutics (cisPt, HU, 5-FU and MTX) has a stronger inhibitory effect on cell growth in tumor cells expressing functional TLR3 as compared with a single treatment. This is a result of TLR3-dependent apoptosis. Conclusion: Our study showed that a combined application of the two agents already being used in tumor therapy could lower the necessary dosage of chemotherapeutics, leading to fewer side effects.
    Keywords Poly(I:C) ; Apoptosis ; Toll-like receptor 3 ; Chemotherapy ; Anticancer therapy
    Language English
    Publishing date 2011-12-22
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Experimental Chemotherapy
    ZDB-ID 6708-8
    ISSN 1421-9794 ; 0009-3157
    ISSN (online) 1421-9794
    ISSN 0009-3157
    DOI 10.1159/000334122
    Database Karger publisher's database

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  7. Article: Analysis of cystic fibrosis gene mutations and associated haplotypes in the Croatian population.

    Knezević, Jelena / Tanacković, Goranka / Matijević, Tanja / Barisić, Ingeborg / Pavelić, Jasminka

    Genetic testing

    2007  Volume 11, Issue 2, Page(s) 133–138

    Abstract: The aim of this study was to reveal the CFTR gene mutation status in the Croatian population as well as to establish the haplotypes associated with cystic fibrosis (CF) and those associated with specific gene mutations. A total of 48 unrelated CF ... ...

    Abstract The aim of this study was to reveal the CFTR gene mutation status in the Croatian population as well as to establish the haplotypes associated with cystic fibrosis (CF) and those associated with specific gene mutations. A total of 48 unrelated CF patients from Croatia were examined. Among 96 tested alleles, we found nine different mutations: DeltaF508, 58.33%; G542X, 3.12%; N1303K, 2.08%; R1162X; 621 + 1G --> T; G85E; Y569C; E585X; and S466X, 1.04%. Analysis of three polymorphic loci revealed 15 different haplotypes. Two of them (21-23-13 and 21-17-13) occurred with a higher frequency (40% and 24%). Both of these haplotypes also carried a CFTR gene mutation (DeltaF508 or G542X) on 27 out of 32 chromosomes. Among 12 (of all together 29) CF alleles on which no mutations were found, we detected 10 different haplotypes. Because there are still no published data on the distribution of polymorphic loci in Croatia, nor haplotypes associated with mutations in the CFTR gene, our results greatly contribute to knowledge regarding the genetic background of CF in this region.
    MeSH term(s) Amino Acid Substitution ; Base Sequence ; Croatia ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; DNA Primers ; Female ; Humans ; Male ; Mutation ; Nuclear Family ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide
    Chemical Substances DNA Primers ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
    Language English
    Publishing date 2007
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1345729-9
    ISSN 1557-7473 ; 1090-6576
    ISSN (online) 1557-7473
    ISSN 1090-6576
    DOI 10.1089/gte.2007.9997
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Induction of CMV-1 promoter by 4-hydroxy-2-nonenal in human embryonic kidney cells.

    Jaganjac, Morana / Matijevic, Tanja / Cindric, Marina / Cipak, Ana / Mrakovcic, Lidija / Gubisch, Wolfgang / Zarkovic, Neven

    Acta biochimica Polonica

    2010  Volume 57, Issue 2, Page(s) 179–183

    Abstract: Oxidative stress, i.e., excessive production of oxygen free radicals and reactive oxygen species, leads to lipid peroxidation and to formation of reactive aldehydes which act as second messengers of free radicals. It has previously been shown that ... ...

    Abstract Oxidative stress, i.e., excessive production of oxygen free radicals and reactive oxygen species, leads to lipid peroxidation and to formation of reactive aldehydes which act as second messengers of free radicals. It has previously been shown that oxidative stress may be involved in the transcriptional regulation of cytomegalovirus (CMV) immediate early promoter, involved in viral reactivation from latency. In the current study we used a plasmid containing the yellow fluorescent protein (YFP) gene under the control of CMV-1 promoter to monitor the influence of hydrogen peroxide and reactive aldehydes, 4-hydroxy-2-nonenal (HNE) and acrolein, on CMV-1 promoter activation in human embryonic kidney cells (HEK293). While acrolein was ineffective, hydrogen peroxide slightly (50 %) stimulated the CMV promoter. In contrast, HNE had a strong, up to 3-fold, enhancing effect on the CMV-1 promoter within four as well as after 24h of treatment. The most effective was the treatment with 24 microM HNE. This effect of HNE suggests that stressful conditions associated with lipid peroxidation could lead to CMV activation.
    MeSH term(s) Aldehydes/pharmacology ; Cell Line ; Cell Survival ; Cysteine Proteinase Inhibitors/pharmacology ; Cytomegalovirus/drug effects ; Cytomegalovirus/genetics ; Humans ; Kidney/cytology ; Promoter Regions, Genetic ; Virus Activation/drug effects
    Chemical Substances Aldehydes ; Cysteine Proteinase Inhibitors ; 4-hydroxy-2-nonenal (K1CVM13F96)
    Language English
    Publishing date 2010
    Publishing country Poland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 595762-x
    ISSN 1734-154X ; 0001-527X
    ISSN (online) 1734-154X
    ISSN 0001-527X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Hottest topics in protein research: MedILS summer school.

    Blaskovic, Sanja / Cretnik, Maja / Juric, Snjezana / Korac, Jelena / Marjanovic, Marko / Matijevic, Tanja

    New biotechnology

    2009  Volume 25, Issue 6, Page(s) 390–391

    MeSH term(s) Chemistry, Analytic/education ; Croatia ; Molecular Probe Techniques ; Proteins/chemistry ; Proteins/metabolism ; Proteomics/education ; Research/education
    Chemical Substances Proteins
    Language English
    Publishing date 2009-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2400836-9
    ISSN 1876-4347 ; 1871-6784
    ISSN (online) 1876-4347
    ISSN 1871-6784
    DOI 10.1016/j.nbt.2009.07.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Genitourinary diseases prior spontaneous abortion as a risk factor for recurrent pregnancy loss.

    Culić, Vida / Konjevoda, Pasko / Mise, Kornelija / Kardum, Goran / Matijević, Tanja / Pavelić, Jasminka

    Collegium antropologicum

    2009  Volume 33, Issue 1, Page(s) 187–192

    Abstract: The etiology of recurrent spontaneous abortion (RSA) is still unexplained. Many couples do not find the cause of their RSA at all. The purpose of this research was to evaluate the association between recurrent pregnancy loss and previous (cured prior to ... ...

    Abstract The etiology of recurrent spontaneous abortion (RSA) is still unexplained. Many couples do not find the cause of their RSA at all. The purpose of this research was to evaluate the association between recurrent pregnancy loss and previous (cured prior to pregnancy) acute/chronic genitourinary infections in both parents. Couples (226) having two or more (up to six) spontaneous abortions were analyzed in this retrospective case-control study. The control group consisted of 124 couples with neither miscarriages nor complicated pregnancies in their past. The data (serum immunological markers, karyotype, flow cytometry data, PHD) were collected from their medical charts. It was found that there was no statistically significant difference in average weeks of pregnancy in which the second, third and fourth abortion occurred. There was a statistically significant difference in previously experienced genitourinary infections between women from the RSA group and the control group, as well as for men from the RSA group and the control group. It can be concluded that past infections of the maternal and/or paternal genitourinary system may be the causal factor for recurrent pregnancy loss and can also pre-determine women that are of greater susceptibility to preterm pregnancy. Therefore the genetic counseling of couples should include thorough medical and family history of both partners and their first- and second-degree relatives in conjunction with typical medical examination.
    MeSH term(s) Abortion, Habitual/etiology ; Adult ; Case-Control Studies ; Female ; Female Urogenital Diseases/complications ; Humans ; Interleukin 1 Receptor Antagonist Protein/genetics ; Male ; Male Urogenital Diseases/complications ; Retrospective Studies ; Risk Factors
    Chemical Substances IL1RN protein, human ; Interleukin 1 Receptor Antagonist Protein
    Language English
    Publishing date 2009-03
    Publishing country Croatia
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 233430-6
    ISSN 0350-6134 ; 0353-3735
    ISSN 0350-6134 ; 0353-3735
    Database MEDical Literature Analysis and Retrieval System OnLINE

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