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Article ; Online: COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3?

Novak Kujundžić, Renata

International journal of molecular sciences

2022 Volume 23, Issue 8

Abstract: Immune response to SARS-CoV-2 and ensuing inflammation pose a huge challenge to the host's nicotinamide adenine dinucleotide ( ... ...

Abstract	Immune response to SARS-CoV-2 and ensuing inflammation pose a huge challenge to the host's nicotinamide adenine dinucleotide (NAD
MeSH term(s)	COVID-19 ; Humans ; NAD/metabolism ; Niacin/pharmacology ; Niacinamide/metabolism ; Pellagra/drug therapy ; Pellagra/etiology ; SARS-CoV-2
Chemical Substances	NAD (0U46U6E8UK) ; Niacinamide (25X51I8RD4) ; Niacin (2679MF687A)
Language	English
Publishing date	2022-04-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23084309
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: EZH2 Inhibition and Cisplatin as a Combination Anticancer Therapy: An Overview of Preclinical Studies.

Samaržija, Ivana / Tomljanović, Marko / Novak Kujundžić, Renata / Trošelj, Koraljka Gall

Cancers

2022 Volume 14, Issue 19

Abstract: Anticancer monotherapies are often insufficient in eradicating cancer cells because cancers are driven by changes in numerous genes and pathways. Combination anticancer therapies which aim to target several cancer traits at once represent a substantial ... ...

Abstract	Anticancer monotherapies are often insufficient in eradicating cancer cells because cancers are driven by changes in numerous genes and pathways. Combination anticancer therapies which aim to target several cancer traits at once represent a substantial improvement in anticancer treatment. Cisplatin is a conventional chemotherapy agent widely used in the treatment of different cancer types. However, the shortcomings of cisplatin use include its toxicity and development of resistance. Therefore, from early on, combination therapies that include cisplatin were considered and used in a variety of cancers. EZH2, an epigenetic regulator, is frequently upregulated in cancers which, in general, potentiates cancer cell malignant behavior. In the past decade, numerous EZH2 inhibitors have been explored for their anticancer properties. In this overview, we present the studies that discuss the joint action of cisplatin and EZH2 inhibitors. According to the data presented, the use of cisplatin and EZH2 inhibitors may be beneficial in the treatment of lung, ovarian, and breast cancers, since there is a substantial amount of published evidence that suggests their concerted action. However, in testicular germ cell tumors, such a combination would not be recommended because cisplatin resistance seems to be associated with decreased expression of EZH2 in this tumor type.
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14194761
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Article ; Online: Curcumin in combined cancer therapy.

Troselj, Koraljka Gall / Kujundzic, Renata Novak

Current pharmaceutical design

2014 Volume 20, Issue 42, Page(s) 6682–6696

Abstract: The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma ... ...

Abstract	The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma longa), influences a wide variety of cellular processes through the reshaping of many molecular targets. One of them, nuclear factor kappa B (NF-κB), represents a strong mediator of inflammation and, in a majority of systems, supports the pro-proliferative features of cancer cells. The application of various anticancer drugs, cytostatics, triggers signals which lead to an increase in cellular NF-κB activity. As a consequence, cancer cells often reshape their survival signaling pathways and, over time, become resistant to applied therapy. Curcumin was shown to be a strong inhibitor of NF-κB activity and its inhibitory effect on NF-κB related pathways often leads to cellular apoptotic response. All these facts, tested and confirmed in many different biological systems, have paved the way for research aimed to elucidate the potential beneficial effects of combining curcumin and various anti-cancer drugs in order to establish more efficient and less toxic cancer treatment modalities. This review addresses certain aspects of NF-κB-related inflammatory response, its role in carcinogenesis and therapy benefits that may be gained through silencing NF-κB by selectively combining curcumin and various anticancer drugs.
MeSH term(s)	Antineoplastic Agents, Phytogenic/chemistry ; Antineoplastic Agents, Phytogenic/isolation & purification ; Antineoplastic Agents, Phytogenic/therapeutic use ; Cell Proliferation/drug effects ; Curcuma/chemistry ; Curcumin/chemistry ; Curcumin/isolation & purification ; Curcumin/therapeutic use ; Humans ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology
Chemical Substances	Antineoplastic Agents, Phytogenic ; NF-kappa B ; Curcumin (IT942ZTH98)
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	10.2174/1381612820666140826154601
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Article ; Online: Polycomb repressive complex's evolutionary conserved function: the role of EZH2 status and cellular background.

Gall Trošelj, Koraljka / Novak Kujundzic, Renata / Ugarkovic, Djurdjica

Clinical epigenetics

2016 Volume 8, Page(s) 55

Abstract: When assembled in multiprotein polycomb repressive complexes (PRCs), highly evolutionary conserved polycomb group (PcG) proteins epigenetically control gene activity. Although the composition of PRCs may vary considerably, it is well established that the ...

Abstract	When assembled in multiprotein polycomb repressive complexes (PRCs), highly evolutionary conserved polycomb group (PcG) proteins epigenetically control gene activity. Although the composition of PRCs may vary considerably, it is well established that the embryonic ectoderm development (EED) 1, suppressor of zeste (SUZ) 12, and methyltransferase enhancer of zeste (EZH2)-containing complex, PRC2, which is abundant in highly proliferative cells (including cancer cells), establishes a repressive methylation mark on histone 3 (H3K27me3). From the perspective of molecular cancer pathogenesis, this effect, when directed towards a promoter of tumor suppressor genes, represents pro-tumorigenic effect. This mode of action was shown in several cancer models. However, EZH2 function extends beyond this scenario. The highly specific cellular background, related to the origin of cell and numerous external stimuli during a given time-window, may be the trigger for EZH2 interaction with other proteins, not necessarily histones. This is particularly relevant for cancer. This review provides a critical overview of the evolutional importance of PRC and discusses several important aspects of EZH2 functioning within PRC. The review also deals with mutational studies on EZH2. Due to the existence of several protein (and messenger RNA (mRNA)) isoforms, these mutations were stratified, using the protein sequence which is considered canonical. This approach showed that there is an urgent need for the uniformed positioning of currently known EZH2 mutations (somatic-in tumors, as well as germline mutations in the Weaver's syndrome). Finally, we discuss EZH2 function with respect to amount of trimethylated H3K27, in a specific cellular milieu, through presenting the most recent data related to EZH2-H3K27m3 relationship in cancer. All these points are significant in considering EZH2 as a therapeutic target.
MeSH term(s)	Enhancer of Zeste Homolog 2 Protein/genetics ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Epigenesis, Genetic ; Histones/metabolism ; Humans ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Polycomb Repressive Complex 2/metabolism
Chemical Substances	Histones ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2016-05-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-016-0226-1
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Article ; Online: Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer.

Novak Kujundžić, Renata / Prpić, Marin / Đaković, Nikola / Dabelić, Nina / Tomljanović, Marko / Mojzeš, Anamarija / Fröbe, Ana / Trošelj, Koraljka Gall

International journal of molecular sciences

2021 Volume 22, Issue 11

Abstract: The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide ( ... ...

Abstract	The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide (NAD
MeSH term(s)	Humans ; Methylation ; NAD/metabolism ; Neoplasm Proteins/metabolism ; Neoplasms/epidemiology ; Neoplasms/therapy ; Neoplastic Stem Cells/enzymology ; Niacinamide/metabolism ; Nicotinamide N-Methyltransferase/metabolism
Chemical Substances	Neoplasm Proteins ; NAD (0U46U6E8UK) ; Niacinamide (25X51I8RD4) ; Nicotinamide N-Methyltransferase (EC 2.1.1.1)
Language	English
Publishing date	2021-05-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22115681
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Article ; Online: Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin.

Mojzeš, Anamarija / Tomljanović, Marko / Milković, Lidija / Kujundžić, Renata Novak / Gašparović, Ana Čipak / Trošelj, Koraljka Gall

International journal of molecular sciences

2020 Volume 21, Issue 5

Abstract: In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate ... ...

Abstract	In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been shown to interact with multiple molecules and signaling pathways in cancer cells, including those relevant for cell metabolism. The effect of curcumin and its solvent, ethanol, was explored on four different cancer cell lines, in which the Warburg effect varied. Vital cellular parameters (proliferation, viability) were measured along with the glucose consumption and lactate production. The transcripts of pyruvate kinase 1 and 2 (PKM1, PKM2), serine hydroxymethyltransferase 2 (SHMT2) and phosphoglycerate dehydrogenase (PHGDH) were quantified with RT-qPCR. The amount and intracellular localization of PKM1, PKM2 and signal transducer and activator of transcription
MeSH term(s)	Cell Line, Tumor ; Curcumin/pharmacology ; Ethanol/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Glucose/metabolism ; Humans ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Lactic Acid/metabolism ; Neoplasms/metabolism ; Protein Kinases/genetics ; Protein Kinases/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; STAT3 Transcription Factor/metabolism ; Transcription, Genetic/drug effects
Chemical Substances	Isoenzymes ; RNA, Messenger ; STAT3 Transcription Factor ; Lactic Acid (33X04XA5AT) ; Ethanol (3K9958V90M) ; Protein Kinases (EC 2.7.-) ; Curcumin (IT942ZTH98) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21051661
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Article ; Online: Implementing Curcumin in Translational Oncology Research.

Trošelj, Koraljka Gall / Samaržija, Ivana / Tomljanović, Marko / Kujundžić, Renata Novak / Đaković, Nikola / Mojzeš, Anamarija

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 22

Abstract: Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are ... ...

Abstract	Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin in clinical oncology. However, the issues regarding timely data reporting and lack of disclosure of the exact curcumin formulations used in these studies should not be neglected. This article is a snapshot of the current status of publicly available data on curcumin clinical trials and a detailed presentation of results obtained so far with some curcumin formulations. Phenomena related to the observed effects of curcumin shown in clinical trials are presented, and its modifying effect on gut microbiota and metabolic reprogramming is discussed. Based on available data, there is a strong indication that curcumin and its metabolites present molecules that do not necessarily need to be abundant in order to act locally and benefit systemically. Future clinical studies should be designed in a way that will take that fact into consideration.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Biological Availability ; Clinical Trials as Topic ; Curcumin/chemistry ; Curcumin/therapeutic use ; Gastrointestinal Microbiome ; Humans ; Interleukin-17/chemistry ; Medical Oncology/trends ; National Institutes of Health (U.S.) ; Neoplasms/drug therapy ; Nicotinamide N-Methyltransferase/chemistry ; Precision Medicine ; Translational Medical Research/trends ; United States
Chemical Substances	Antineoplastic Agents ; IL17A protein, human ; Interleukin-17 ; Nicotinamide N-Methyltransferase (EC 2.1.1.1) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2020-11-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25225240
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Article ; Online: Curcumin and its Potential for Systemic Targeting of Inflamm-Aging and Metabolic Reprogramming in Cancer.

Kujundžić, Renata Novak / Stepanić, Višnja / Milković, Lidija / Gašparović, Ana Čipak / Tomljanović, Marko / Trošelj, Koraljka Gall

International journal of molecular sciences

2019 Volume 20, Issue 5

Abstract: Pleiotropic effects of curcumin have been the subject of intensive research. The interest in this molecule for preventive medicine may further increase because of its potential to modulate inflamm-aging. Although direct data related to its effect on ... ...

Abstract	Pleiotropic effects of curcumin have been the subject of intensive research. The interest in this molecule for preventive medicine may further increase because of its potential to modulate inflamm-aging. Although direct data related to its effect on inflamm-aging does not exist, there is a strong possibility that its well-known anti-inflammatory properties may be relevant to this phenomenon. Curcumin's binding to various proteins, which was shown to be dependent on cellular oxidative status, is yet another feature for exploration in depth. Finally, the binding of curcumin to various metabolic enzymes is crucial to curcumin's interference with powerful metabolic machinery, and can also be crucial for metabolic reprogramming of cancer cells. This review offers a synthesis and functional links that may better explain older data, some observational, in light of the most recent findings on curcumin. Our focus is on its modes of action that have the potential to alleviate specific morbidities of the 21st century.
MeSH term(s)	Aging/drug effects ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Curcuma/chemistry ; Curcumin/chemistry ; Curcumin/pharmacology ; Curcumin/therapeutic use ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Inflammation/metabolism ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/metabolism ; Oxidative Stress/drug effects
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Antineoplastic Agents ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2019-03-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20051180
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Article ; Online: Implementing Curcumin in Translational Oncology Research

Koraljka Gall Trošelj / Ivana Samaržija / Marko Tomljanović / Renata Novak Kujundžić / Nikola Đaković / Anamarija Mojzeš

Molecules, Vol 25, Iss 5240, p

2020 Volume 5240

Abstract	Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin in clinical oncology. However, the issues regarding timely data reporting and lack of disclosure of the exact curcumin formulations used in these studies should not be neglected. This article is a snapshot of the current status of publicly available data on curcumin clinical trials and a detailed presentation of results obtained so far with some curcumin formulations. Phenomena related to the observed effects of curcumin shown in clinical trials are presented, and its modifying effect on gut microbiota and metabolic reprogramming is discussed. Based on available data, there is a strong indication that curcumin and its metabolites present molecules that do not necessarily need to be abundant in order to act locally and benefit systemically. Future clinical studies should be designed in a way that will take that fact into consideration.
Keywords	cancer therapy ; clinical trials ; microbiota ; IL-17 ; nicotinamide N -methyltransferase ; metabolic reprogramming ; Organic chemistry ; QD241-441
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Pyridine nucleotides in regulation of cell death and survival by redox and non-redox reactions.

Novak Kujundžić, Renata / Žarković, Neven / Gall Trošelj, Koraljka

Critical reviews in eukaryotic gene expression

2014 Volume 24, Issue 4, Page(s) 287–309

Abstract: Changes of the level and ratios of pyridine nucleotides determine metabolism- dependent cellular redox status and the activity of poly(ADP-ribose) polymerases (PARPs) and sirtuins, thereby influencing several processes closely related to cell survival ... ...

Abstract	Changes of the level and ratios of pyridine nucleotides determine metabolism- dependent cellular redox status and the activity of poly(ADP-ribose) polymerases (PARPs) and sirtuins, thereby influencing several processes closely related to cell survival and death. Pyridine nucleotides participate in numerous metabolic reactions whereby their net cellular level remains constant, but the ratios of NAD+/NADP+ and NADH/NADPH oscillate according to metabolic changes in response to diverse stress signals. In non-redox reactions, NAD+ is degraded and quickly, afterward, resynthesized in the NAD+ salvage pathway, unless overwhelming activation of PARP-1 consumes NAD+ to the point of no return, when the cell can no longer generate enough ATP to accommodate NAD+ resynthesis. The activity of PARP-1 is mandatory for the onset of cytoprotective autophagy on sublethal stress signals. It has become increasingly clear that redox status, largely influenced by the metabolism-dependent composition of the pyridine nucleotides pool, plays an important role in the synthesis of pro-apoptotic and anti-apoptotic sphingolipids. Awareness of the involvement of the prosurvival sphingolipid, sphingosine-1-phosphate, in transition from inflammation to malignant transformation has recently emerged. Here, the participation of pyridine nucleotides in redox and non-redox reactions, sphingolipid metabolism, and their role in cell fate decisions is reviewed.
MeSH term(s)	Cell Death ; Cell Survival ; Nucleotides/metabolism ; Oxidation-Reduction ; Pyridines/metabolism ; Sphingolipids/metabolism
Chemical Substances	Nucleotides ; Pyridines ; Sphingolipids
Language	English
Publishing date	2014-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1071345-1
ISSN	1045-4403
ISSN	1045-4403
DOI	10.1615/critreveukaryotgeneexpr.2014011828
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