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Article ; Online: Editorial: combined cancer therapy.

Pavelic, Jasminka

2014 Volume 20, Issue 42, Page(s) 6511–6512

MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology
Language	English
Publishing date	2014-09-01
Publishing country	United Arab Emirates
Document type	Editorial ; Introductory Journal Article
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612820666140826154834
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Article ; Online: ESTIMATION OF AIRBORNE 106RU ACTIVITY CONCENTRATION FROM TOTAL BETA ACTIVITY OF PM10 PARTICLE FRACTIONS.

Suric Mihic, Marija / Beslic, Ivan / Davila, Silvije / Marovic, Gordana / Pavelić, Luka / Sencar, Jasminka

Radiation protection dosimetry

2020 Volume 189, Issue 4, Page(s) 497–504

Abstract: Airborne radioruthenium, as a result of an accidental release, presents a risk for occupational and public exposure. In fall 2017, a detection of 106Ru was reported by the European atmospheric radioactive contamination monitoring networks. We ... ...

Abstract	Airborne radioruthenium, as a result of an accidental release, presents a risk for occupational and public exposure. In fall 2017, a detection of 106Ru was reported by the European atmospheric radioactive contamination monitoring networks. We investigated the daily specific total beta activity of PM10 particle fractions samples. The presented method enables indirect determination of airborne 106Ru activity concentration from total beta activity, in case 106Ru was confirmed as single excess radiological pollutant. This allows for daily measurements and time-resolved 106Ru activity concentration data. We estimated the indicative committed effective dose due to 106Ru inhalation for the Croatian population during the exposure period. Although the estimated dose value of ~169.7 nSv, for ~6-d duration of ruthenium air pollution, was very low, it was ~40 times higher than the value for Hinh from inhalation of other radionuclides (90Sr + 137Cs + 40K + 7Be).
MeSH term(s)	Beryllium ; Cesium Radioisotopes ; Radioisotopes ; Ruthenium Radioisotopes/analysis ; Strontium Radioisotopes
Chemical Substances	Beryllium-7 ; Cesium Radioisotopes ; Radioisotopes ; Ruthenium Radioisotopes ; Ruthenium-106 ; Strontium Radioisotopes ; Cesium-137 (4T2E65IAR7) ; Strontium-90 (5TZZ77Z4ER) ; Beryllium (OW5102UV6N)
Language	English
Publishing date	2020-08-24
Publishing country	England
Document type	Journal Article
ZDB-ID	225912-6
ISSN	1742-3406 ; 0144-8420
ISSN (online)	1742-3406
ISSN	0144-8420
DOI	10.1093/rpd/ncaa067
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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
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Zs.A 1598: Show issues

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Article ; Online: Recent Findings on the Application of Toll-like Receptors Agonists in Cancer Therapy.

Mikulandra, Martina / Pavelic, Jasminka / Glavan, Tanja Matijevic

Current medicinal chemistry

2017 Volume 24, Issue 19, Page(s) 2011–2032

Abstract: The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs) ...

Abstract	The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The most extensively studied family of PRRs is Toll-like receptors (TLRs), which can trigger various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as there are many different studies showing contradictory results. TLRs have been associated with both tumor progression and immunosuppression as well as with apoptosis and immune system activation. With their ability to induce apoptotic response and activation of innate and adaptive immunity, TLRs are an interesting pharmacological target for the development of anticancer therapy. There are numerous studies including the clinical trials reviewed in this paper, indicating that TLR agonists, especially combined with other more conventional therapies such as chemotherapy and radiotherapy, are promising adjuvants or components of newly developed treatment regimens. Still, the increasing number of studies indicating protumorigenic consequences of TLR activation in various cancer types and recent reports of the existence of endogenous TLR ligands, forewarn that more studies on this topic are required before their inclusion into regular clinical practice.
MeSH term(s)	Adaptive Immunity/drug effects ; Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Clinical Trials as Topic ; Drug Discovery ; Humans ; Immunity, Innate/drug effects ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/immunology ; Signal Transduction/drug effects ; Toll-Like Receptors/agonists ; Toll-Like Receptors/immunology
Chemical Substances	Antineoplastic Agents ; Toll-Like Receptors
Language	English
Publishing date	2017
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0929867324666170320114359
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Zs.A 4432: Show issues

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Article ; Online: The exploitation of Toll-like receptor 3 signaling in cancer therapy.

Glavan, Tanja Matijevic / Pavelic, Jasminka

Current pharmaceutical design

2014 Volume 20, Issue 42, Page(s) 6555–6564

Abstract: Toll-like receptors (TLRs) are a group of transmembrane receptors that recognize molecular motifs of pathogen origin and activate immune response. Although TLRs were first identified in immune system cells, recent studies show they can also be expressed ... ...

Abstract	Toll-like receptors (TLRs) are a group of transmembrane receptors that recognize molecular motifs of pathogen origin and activate immune response. Although TLRs were first identified in immune system cells, recent studies show they can also be expressed in tumor cells. TLR3 recognizes dsRNA or its synthetic ligand poly (I: C) and is responsible primarily for the defense against viral infections. Recent studies showed that TLR3 can trigger apoptosis in cancer cell. Furthermore, other dsRNA binding receptors (MDA5 and RIG-I), localized in cytoplasm, can also bind poly (I: C) and therefore contribute to this effect. With TLR3's capacity to induce apoptosis and activate the immune system at the same time, TLR3 ligands are an attractive therapeutic option for treatment of cancer. Novel therapies include combining poly (I: C) with other components such as chemotherapeutics, apoptosis enhancers, other TLR ligands and peptides activating the immune system. Slightly modified TLR3 agonists (Ampligen®, Hiltonol®, poly IC-LC) are already being used in clinical studies for cancer therapy as single agents or in combination with other drugs. On the other hand, latest studies forewarn that TLR3 activation can also have tumor promoting role so it is crucial to identify the terms by which TLR3 has pro-tumor/anti-tumor effect in order to safely implement TLR3 ligand based therapy into clinical trials.
MeSH term(s)	Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Signal Transduction/drug effects ; Toll-Like Receptor 3/agonists ; Toll-Like Receptor 3/metabolism
Chemical Substances	Toll-Like Receptor 3
Language	English
Publishing date	2014-09-01
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612820666140826153347
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Article ; Online: Serum vitamin D levels in children with newly diagnosed and chronic immune thrombocytopenia.

Čulić, Srđana / Markić, Joško / Petrović, Davor / Konjevoda, Paško / Pavelić, Jasminka

Seminars in hematology

2016 Volume 53 Suppl 1, Page(s) S67–9

Abstract: The primary objective of the study was to assess the vitamin D (VD) status of patients suffering from ITP. Children from the case cohort (total 21) were recruited from chronic ITP patients (followed as outpatients) and newly diagnosed ITP (prospective ... ...

Abstract	The primary objective of the study was to assess the vitamin D (VD) status of patients suffering from ITP. Children from the case cohort (total 21) were recruited from chronic ITP patients (followed as outpatients) and newly diagnosed ITP (prospective study) patients. VD deficiency (values <75 nmol/L) was detected in 11 patients with newly diagnosed ITP, and seven patients with chronic ITP. Only three patients with newly diagnosed, and none with chronic ITP had normal VD values. Newly diagnosed ITP patients had statistically significantly higher values (P <.044) of VD than the patients with chronic type of ITP. Platelets values did not follow VD level. VD deficiency is very common in children with either newly diagnosed or chronic ITP form. Therefore there is a utility supplementing VD in these patients. To investigate the role of VD as an immune modulating drug for patients with ITP, a prospective randomized placebo-controlled trial needs to be performed.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Cohort Studies ; Female ; Humans ; Male ; Purpura, Thrombocytopenic, Idiopathic/blood ; Purpura, Thrombocytopenic, Idiopathic/immunology ; Vitamin D/blood
Chemical Substances	Vitamin D (1406-16-2)
Language	English
Publishing date	2016-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	206923-4
ISSN	1532-8686 ; 0037-1963
ISSN (online)	1532-8686
ISSN	0037-1963
DOI	10.1053/j.seminhematol.2016.04.020
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Zs.A 328: Show issues

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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
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Zs.A 1855: Show issues

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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
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Article ; Online: Immune thrombocytopenia: serum cytokine levels in children and adults.

Culić, Srđana / Salamunić, Ilza / Konjevoda, Paško / Dajak, Slavica / Pavelić, Jasminka

Medical science monitor : international medical journal of experimental and clinical research

2013 Volume 19, Page(s) 797–801

Abstract: Background: Immune thrombocytopenia (ITP) is an immune-mediated platelet disorder in which autoantibody-coated platelets are removed from the blood by monocytic phagocytes and there is impaired platelet production. There is a delicate balance of ... ...

Abstract	Background: Immune thrombocytopenia (ITP) is an immune-mediated platelet disorder in which autoantibody-coated platelets are removed from the blood by monocytic phagocytes and there is impaired platelet production. There is a delicate balance of specific cytokine levels, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. This study was designed to investigate the differences in Th cytokine levels between children and adults with newly diagnosed ITP and to compare these profiles to those found in healthy, age-matched controls. Material/methods: The concentration of IL-1alpha, IL-2, IL-3, IL-4, IL-6, IL-10, TNF-alpha, IFN-alpha, and IFN-alpha in serum specimens was analyzed by enzyme-linked immunosorbent assay. Results: At the time of ITP diagnosis, children showed significantly lower serum levels of interleukin IL-2 and tumor necrosis factor TNF-alpha and higher serum level of IL-3 than healthy controls. Serum level of IL-4 in adult ITP patients was higher than those in control subjects. When compared with adults, children with ITP had lower serum level of IL-4, IL-6 and IFN-alpha, and higher level of IFN-alpha. Conclusions: Significant differences in serum cytokine levels between pediatric patients and healthy controls indicate that cytokine disturbances--especially changes in IL-2, IL-3 and TNF-alpha--might be involved in the pathogenesis of newly diagnosed ITP. TNF-alpha is the most informative variable for discrimination between healthy children and those with ITP.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Croatia ; Cytokines/blood ; Enzyme-Linked Immunosorbent Assay ; Humans ; Infant ; Interferons/blood ; Interleukins/blood ; Middle Aged ; Multivariate Analysis ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic/blood ; Tumor Necrosis Factor-alpha/blood
Chemical Substances	Cytokines ; Interleukins ; Tumor Necrosis Factor-alpha ; Interferons (9008-11-1)
Language	English
Publishing date	2013-09-27
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1439041-3
ISSN	1643-3750 ; 1234-1010
ISSN (online)	1643-3750
ISSN	1234-1010
DOI	10.12659/MSM.884017
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Article ; Online: Toll-like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF.

Matijevic Glavan, Tanja / Cipak Gasparovic, Ana / Vérillaud, Benjamin / Busson, Pierre / Pavelic, Jasminka

Molecular carcinogenesis

2017 Volume 56, Issue 4, Page(s) 1214–1226

Abstract: Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a ... ...

Abstract	Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line, leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS), and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2), and CD44 variants, which were over-expressed after TLR3 stimulation. TLR3 activation also induced upregulation of different genes involved in cancer progression (VEGF, MMP9, uPAR) and enzymes involved in glycolytic pathway. Most of the observed effects were Myc-dependent; however, some of them were also connected with MAPK and HIF signaling pathways. Since TLR3 agonists are being investigated as potential novel cancer therapy adjuvants and apoptosis inducers, alone or in combination with other therapeutic options, data presented here suggest extreme caution before their introduction into clinical practice. The fact that TLR3 ligands [poly(I:C) and poly(A:U)] can also aid cancer survival and progression, through induction of metabolic reprogramming, emphasizes the need to investigate this particular topic. Our data suggest that the combination of TLR3 ligands with Myc or MAPK inhibitors may be a way to neutralize their undesirable effects while enhancing their anti-tumor effect. © 2016 Wiley Periodicals, Inc.
MeSH term(s)	Cell Line, Tumor ; Cell Movement ; Glycolysis ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; MAP Kinase Signaling System ; Oxidative Stress ; Pharyngeal Neoplasms/metabolism ; Pharyngeal Neoplasms/pathology ; Pharynx/metabolism ; Pharynx/pathology ; Poly I-C/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Toll-Like Receptor 3/metabolism
Chemical Substances	Hypoxia-Inducible Factor 1 ; Proto-Oncogene Proteins c-myc ; Reactive Oxygen Species ; TLR3 protein, human ; Toll-Like Receptor 3 ; Poly I-C (O84C90HH2L)
Language	English
Publishing date	2017-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1004029-8
ISSN	1098-2744 ; 0899-1987
ISSN (online)	1098-2744
ISSN	0899-1987
DOI	10.1002/mc.22584
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