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Article ; Online: Human Vault RNAs: Exploring Their Potential Role in Cellular Metabolism.

Taube, Magdalena / Lisiak, Natalia / Totoń, Ewa / Rubiś, Błażej

International journal of molecular sciences

2024 Volume 25, Issue 7

Abstract: Non-coding RNAs have been described as crucial regulators of gene expression and guards of cellular homeostasis. Some recent papers focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, ... ...

Abstract	Non-coding RNAs have been described as crucial regulators of gene expression and guards of cellular homeostasis. Some recent papers focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which makes them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complexes. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that resembles a vault. Their sequence and structure are highly evolutionarily conserved and show many similarities in comparison with different species, but vault RNAs have various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.
MeSH term(s)	Humans ; Genome, Human ; Carcinogenesis ; Cell Transformation, Neoplastic ; Apoptosis ; RNA/genetics
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2024-04-06
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/ijms25074072
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cytotoxic effects of kinetin riboside and its selected analogues on cancer cell lines.

Totoń, Ewa / Lisiak, Natalia / Romaniuk-Drapała, Aleksandra / Framski, Grzegorz / Wyszko, Eliza / Ostrowski, Tomasz

Bioorganic & medicinal chemistry letters

2024 Volume 100, Page(s) 129628

Abstract: ... ...

Abstract	N
MeSH term(s)	Humans ; Female ; Apoptosis ; Cell Line, Tumor ; Ovarian Neoplasms ; Adenosine/pharmacology ; Antineoplastic Agents/pharmacology ; Furans/pharmacology ; Kinetin
Chemical Substances	kinetin riboside ; Adenosine (K72T3FS567) ; Antineoplastic Agents ; Furans ; Kinetin (P39Y9652YJ)
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2024.129628
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Article ; Online: The Role of Telomerase in Breast Cancer's Response to Therapy.

Judasz, Eliza / Lisiak, Natalia / Kopczyński, Przemysław / Taube, Magdalena / Rubiś, Błażej

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: Currently, breast cancer appears to be the most widespread cancer in the world and the most common cause of cancer deaths. This specific type of cancer affects women in both developed and developing countries. Prevention and early diagnosis are very ... ...

Abstract	Currently, breast cancer appears to be the most widespread cancer in the world and the most common cause of cancer deaths. This specific type of cancer affects women in both developed and developing countries. Prevention and early diagnosis are very important factors for good prognosis. A characteristic feature of cancer cells is the ability of unlimited cell division, which makes them immortal. Telomeres, which are shortened with each cell division in normal cells, are rebuilt in cancer cells by the enzyme telomerase, which is expressed in more than 85% of cancers (up to 100% of adenocarcinomas, including breast cancer). Telomerase may have different functions that are related to telomeres or unrelated. It has been shown that high activity of the enzyme in cancer cells is associated with poor cell sensitivity to therapies. Therefore, telomerase has become a potential target for cancer therapies. The low efficacy of therapies has resulted in the search for new combined and more effective therapeutic methods, including the involvement of telomerase inhibitors and telomerase-targeted immunotherapy.
MeSH term(s)	Female ; Humans ; Telomerase/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Telomere/metabolism ; Immunotherapy ; Neoplasms/pathology ; Enzyme Inhibitors/therapeutic use
Chemical Substances	Telomerase (EC 2.7.7.49) ; Enzyme Inhibitors
Language	English
Publishing date	2022-10-25
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/ijms232112844
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Article: Synthesis, Cytotoxicity and Molecular Docking of New Hybrid Compounds by Combination of Curcumin with Oleanolic Acid.

Sowa-Kasprzak, Katarzyna / Totoń, Ewa / Kujawski, Jacek / Olender, Dorota / Lisiak, Natalia / Zaprutko, Lucjusz / Rubiś, Błażej / Kaczmarek, Mariusz / Pawełczyk, Anna

Biomedicines

2023 Volume 11, Issue 6

Abstract: Curcumin and oleanolic acid are natural compounds with high potential in medicinal chemistry. These products have been widely studied for their pharmacological properties and have been structurally modified to improve their bioavailability and ... ...

Abstract	Curcumin and oleanolic acid are natural compounds with high potential in medicinal chemistry. These products have been widely studied for their pharmacological properties and have been structurally modified to improve their bioavailability and therapeutic value. In the present study, we discuss how these compounds are utilized to develop bioactive hybrid compounds that are intended to target cancer cells. Using a bifunctional linker, succinic acid, to combine curcumin and triterpenoic oleanolic acid, several hybrid compounds were prepared. Their cytotoxicity against different cancer cell lines was evaluated and compared with the activity of curcumin (the IC50 value (24 h), for MCF7, HeLaWT and HT-29 cancer cells for
Language	English
Publishing date	2023-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11061506
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Article ; Online: Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR.

Lisiak, Natalia / Dzikowska, Patrycja / Wisniewska, Urszula / Kaczmarek, Mariusz / Bednarczyk-Cwynar, Barbara / Zaprutko, Lucjusz / Rubis, Blazej

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Breast cancer is one of the most frequently observed malignancies worldwide and represents a heterogeneous group of cancers. For this reason, it is crucial to properly diagnose every single case so a specific and efficient therapy can be adjusted. One of ...

Abstract	Breast cancer is one of the most frequently observed malignancies worldwide and represents a heterogeneous group of cancers. For this reason, it is crucial to properly diagnose every single case so a specific and efficient therapy can be adjusted. One of the most critical diagnostic parameters evaluated in cancer tissue is the status of the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). Interestingly, the expression of the indicated receptors may be used in a personalized therapy approach. Importantly, the promising role of phytochemicals in the modulation of pathways controlled by ER and EGFR was also demonstrated in several types of cancer. One such biologically active compound is oleanolic acid, but due to poor water solubility and cell membrane permeability that limits its use, alternative derivative compounds were developed. These are HIMOXOL and Br-HIMOLID, which were demonstrated to be capable of inducing apoptosis and autophagy or diminishing the migratory and invasive potential of breast cancer cells in vitro. In our study, we revealed that proliferation, cell cycle, apoptosis, autophagy, and also the migratory potential of HIMOXOL and Br-HIMOLID in breast cancer cells are mediated by ER (MCF7) and EGFR (MDA-MB-231) receptors. These observations make the studied compounds interesting in the context of anticancer strategies.
MeSH term(s)	Humans ; Female ; Receptors, Estrogen ; Oleanolic Acid/pharmacology ; Breast Neoplasms/metabolism ; ErbB Receptors/metabolism ; Apoptosis ; Cell Proliferation ; Cell Line, Tumor
Chemical Substances	Receptors, Estrogen ; methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate ; 12-bromo-3-hydroxyimonoolean-28-13-olide ; Oleanolic Acid (6SMK8R7TGJ) ; ErbB Receptors (EC 2.7.10.1) ; EGFR protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-03-07
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/ijms24065099
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Article ; Online: miRNA Expression Profiling in Human Breast Cancer Diagnostics and Therapy.

Dziechciowska, Iga / Dąbrowska, Małgorzata / Mizielska, Anna / Pyra, Natalia / Lisiak, Natalia / Kopczyński, Przemysław / Jankowska-Wajda, Magdalena / Rubiś, Błażej

Current issues in molecular biology

2023 Volume 45, Issue 12, Page(s) 9500–9525

Abstract: Breast cancer is one of the most commonly diagnosed cancer types worldwide. Regarding molecular characteristics and classification, it is a heterogeneous disease, which makes it more challenging to diagnose. As is commonly known, early detection plays a ... ...

Abstract	Breast cancer is one of the most commonly diagnosed cancer types worldwide. Regarding molecular characteristics and classification, it is a heterogeneous disease, which makes it more challenging to diagnose. As is commonly known, early detection plays a pivotal role in decreasing mortality and providing a better prognosis for all patients. Different treatment strategies can be adjusted based on tumor progression and molecular characteristics, including personalized therapies. However, dealing with resistance to drugs and recurrence is a challenge. The therapeutic options are limited and can still lead to poor clinical outcomes. This review aims to shed light on the current perspective on the role of miRNAs in breast cancer diagnostics, characteristics, and prognosis. We discuss the potential role of selected non-coding RNAs most commonly associated with breast cancer. These include miR-21, miR-106a, miR-155, miR-141, let-7c, miR-335, miR-126, miR-199a, miR-101, and miR-9, which are perceived as potential biomarkers in breast cancer prognosis, diagnostics, and treatment response monitoring. As miRNAs differ in expression levels in different types of cancer, they may provide novel cancer therapy strategies. However, some limitations regarding dynamic alterations, tissue-specific profiles, and detection methods must also be raised.
Language	English
Publishing date	2023-11-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2000024-8
ISSN	1467-3045 ; 1467-3037
ISSN (online)	1467-3045
ISSN	1467-3037
DOI	10.3390/cimb45120595
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Article ; Online: Doxorubicin and Cisplatin Modulate miR-21, miR-106, miR-126, miR-155 and miR-199 Levels in MCF7, MDA-MB-231 and SK-BR-3 Cells That Makes Them Potential Elements of the DNA-Damaging Drug Treatment Response Monitoring in Breast Cancer Cells-A Preliminary Study.

Mizielska, Anna / Dziechciowska, Iga / Szczepański, Radosław / Cisek, Małgorzata / Dąbrowska, Małgorzata / Ślężak, Jan / Kosmalska, Izabela / Rymarczyk, Marta / Wilkowska, Klaudia / Jacczak, Barbara / Totoń, Ewa / Lisiak, Natalia / Kopczyński, Przemysław / Rubiś, Błażej

Genes

2023 Volume 14, Issue 3

Abstract: One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate ...

Abstract	One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in selected miRNA levels in various breast cancer cell lines (MCF7, MDA-MB-231, SK-BR-3) treated with doxorubicin or cisplatin. The selection was based on literature data regarding the most commonly altered miRNAs in breast cancer (21-3p, 21-5p, 106a-5p, 126-3p, 126-5p, 155-3p, 155-5p, 199b-3p, 199b-5p, 335-3p, 335-5p). qPCR assessment revealed significant differences in the basal levels of some miRNAs in respective cell lines, with the most striking difference in miR-106a-5p, miR-335-5p and miR-335-3p-all of them were lowest in MCF7, while miR-153p was not detected in SK-BR-3. Additionally, different alterations of selected miRNAs were observed depending on the cell line and the drug. However, regardless of these variables, 21-3p/-5p, 106a, 126-3p, 155-3p and 199b-3p miRNAs were shown to respond either to doxorubicin or to cisplatin treatment. These miRNAs seem to be good candidates for markers of breast cancer cell response to doxorubicin or cisplatin. Especially since some earlier reports suggested their role in affecting pathways and expression of genes associated with the DNA-damage response. However, it must be emphasized that the preliminary study shows effects that may be highly related to the applied drug itself and its concentration. Thus, further examination, including human samples, is required.
MeSH term(s)	Humans ; Female ; Cisplatin/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Doxorubicin/pharmacology ; MCF-7 Cells ; DNA
Chemical Substances	Cisplatin (Q20Q21Q62J) ; MicroRNAs ; Doxorubicin (80168379AG) ; DNA (9007-49-2) ; MIRN106 microRNA, human ; MIRN126 microRNA, human ; MIRN155 microRNA, human ; mirn199 microRNA, human ; MIRN21 microRNA, human
Language	English
Publishing date	2023-03-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030702
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Article ; Online: Autophagy as a Potential Therapeutic Target in Breast Cancer Treatment.

Lisiak, Natalia / Toton, Ewa / Rybczynska, Maria

Current cancer drug targets

2017 Volume 18, Issue 7, Page(s) 629–639

Abstract: One of the crucial reasons of breast cancer therapy failure is an impairment of mechanisms responsible for metabolism and cellular homeostasis, which makes it difficult to foresee the response to the treatment. Targeted therapy in breast cancer is ... ...

Abstract	One of the crucial reasons of breast cancer therapy failure is an impairment of mechanisms responsible for metabolism and cellular homeostasis, which makes it difficult to foresee the response to the treatment. Targeted therapy in breast cancer is dictated by the expression of specific molecules such as growth factor or hormone receptors. Many types of breast cancer exhibit different abnormalities in the apoptotic pathway, which confer the resistance to many forms of chemotherapy. Because of the fundamental importance of autophagy in the development and progression of cancer and its ability to affect treatment response, there has been an immense research on molecular regulation and signal transduction mechanisms that control this process. Here, we summarize the present knowledge concerning different breast cancer treatment strategies using drugs approved for the treatment of different breast cancer molecular subtypes with targeting pathways and factors associated with autophagy modulation/ regulation.
MeSH term(s)	Autophagosomes/metabolism ; Autophagy ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Drug Resistance, Neoplasm ; ErbB Receptors/metabolism ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Molecular Targeted Therapy ; Receptor, ErbB-2/metabolism ; Signal Transduction
Chemical Substances	ESR1 protein, human ; Estrogen Receptor alpha ; EGFR protein, human (EC 2.7.10.1) ; ERBB2 protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2017-11-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2064824-8
ISSN	1873-5576 ; 1568-0096
ISSN (online)	1873-5576
ISSN	1568-0096
DOI	10.2174/1568009617666171114143330
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Article ; Online: Doxorubicin and Cisplatin Modulate miR-21, miR-106, miR-126, miR-155 and miR-199 Levels in MCF7, MDA-MB-231 and SK-BR-3 Cells That Makes Them Potential Elements of the DNA-Damaging Drug Treatment Response Monitoring in Breast Cancer Cells—A Preliminary Study

Mizielska, Anna / Dziechciowska, Iga / Szczepański, Radosław / Cisek, Małgorzata / Dąbrowska, Małgorzata / Slezák, Ján / Kosmalska, Izabela / Rymarczyk, Marta / Wilkowska, Klaudia / Jacczak, Barbara / Totoń, Ewa / Lisiak, Natalia / Kopczyński, Przemysław / Rubiś, Błażej

Genes (Basel). 2023 Mar. 12, v. 14, no. 3

2023

Abstract	One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in selected miRNA levels in various breast cancer cell lines (MCF7, MDA-MB-231, SK-BR-3) treated with doxorubicin or cisplatin. The selection was based on literature data regarding the most commonly altered miRNAs in breast cancer (21-3p, 21-5p, 106a-5p, 126-3p, 126-5p, 155-3p, 155-5p, 199b-3p, 199b-5p, 335-3p, 335-5p). qPCR assessment revealed significant differences in the basal levels of some miRNAs in respective cell lines, with the most striking difference in miR-106a-5p, miR-335-5p and miR-335-3p—all of them were lowest in MCF7, while miR-153p was not detected in SK-BR-3. Additionally, different alterations of selected miRNAs were observed depending on the cell line and the drug. However, regardless of these variables, 21-3p/-5p, 106a, 126-3p, 155-3p and 199b-3p miRNAs were shown to respond either to doxorubicin or to cisplatin treatment. These miRNAs seem to be good candidates for markers of breast cancer cell response to doxorubicin or cisplatin. Especially since some earlier reports suggested their role in affecting pathways and expression of genes associated with the DNA-damage response. However, it must be emphasized that the preliminary study shows effects that may be highly related to the applied drug itself and its concentration. Thus, further examination, including human samples, is required.
Keywords	DNA damage ; breast neoplasms ; cell lines ; cisplatin ; doxorubicin ; drug therapy ; humans ; microRNA ; neoplasm cells
Language	English
Dates of publication	2023-0312
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030702
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Article ; Online: Oleanolic Acid's Semisynthetic Derivatives HIMOXOL and Br-HIMOLID Show Proautophagic Potential and Inhibit Migration of HER2-Positive Breast Cancer Cells In Vitro.

Lisiak, Natalia Magdalena / Lewicka, Izabela / Kaczmarek, Mariusz / Kujawski, Jacek / Bednarczyk-Cwynar, Barbara / Zaprutko, Lucjusz / Rubis, Blazej

International journal of molecular sciences

2021 Volume 22, Issue 20

Abstract: Approximately 20-30% of the diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). This type of cancer is associated with a more aggressive phenotype; thus, there is a need for the discovery of new compounds that would ... ...

Abstract	Approximately 20-30% of the diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). This type of cancer is associated with a more aggressive phenotype; thus, there is a need for the discovery of new compounds that would improve the survival in HER2-positive breast cancer patients. It seems that one of the most promising therapeutic cancer strategies could be based on the biological activity of pentacyclic triterpenes' derivatives and the best-known representative of this group, oleanolic acid (OA). The biological activity of oleanolic acid and its two semisynthetic derivatives, methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL) and 12α-bromo-3-hydroxyimonoolean-28→13-olide (Br-HIMOLID), was assessed in SK-BR-3 breast cancer cells (HER2-positive). Viability tests, cell cycle assessment, evaluation of apoptosis, autophagy, and adhesion/migration processes were performed using MTT, clonogenic, cytofluorometry, Western blot, and qPCR. Both derivatives revealed higher cytotoxicity in studied breast cancer cells than the maternal compound, OA. They also decreased cell viability, induced autophagy, and (when applied in sub-cytotoxic concentrations) decreased the migration of SK-BR-3 cells.This study is the first to report the cytostatic, proautophagic (mTOR/LC3/SQSTM/BECN1 pathway), and anti-migratory (integrin β1/FAK/paxillin pathway) activities of HIMOXOL and Br-HIMOLID in HER2-positive breast cancer cells.
MeSH term(s)	Apoptosis ; Autophagy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Female ; Humans ; In Vitro Techniques ; Oleanolic Acid/analogs & derivatives ; Oleanolic Acid/chemistry ; Oleanolic Acid/pharmacology ; Receptor, ErbB-2/metabolism ; Tumor Cells, Cultured
Chemical Substances	12-bromo-3-hydroxyimonoolean-28-13-olide ; methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate ; Oleanolic Acid (6SMK8R7TGJ) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2021-10-19
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/ijms222011273
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