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Article ; Online: Effects of lower screening activity during the COVID-19 pandemic on breast cancer patient pathways: Evidence from the age cut-off of organized screening.

Elek, Péter / Fadgyas-Freyler, Petra / Váradi, Balázs / Mayer, Balázs / Zemplényi, Antal / Csanádi, Marcell

2022 Volume 126, Issue 8, Page(s) 763–769

Abstract: We examined the effects of the COVID-19 pandemic on the screening, diagnosis and treatment of breast cancer in Hungary based on administrative data until June 2021, covering three pandemic waves. After correcting for trend and seasonality, the number of ... ...

Abstract	We examined the effects of the COVID-19 pandemic on the screening, diagnosis and treatment of breast cancer in Hungary based on administrative data until June 2021, covering three pandemic waves. After correcting for trend and seasonality, the number of mammography examinations decreased by 68% in 2020q2, was around its usual level in 2020q3 and was reduced by 20-35% throughout 2020q4-2021q2. The reduction was caused by a combination of supply-side (temporary suspensions of screening) and demand-side (lower screening participation during the pandemic waves) factors. The number of new breast cancer diagnoses and mastectomy surgeries responded with a lag, and were below their usual level by 15-30% in all quarters between 2020q2 and 2021q2, apart from 2020q4, when there was no significant difference. Using a regression discontinuity framework, we found that the partial mastectomy rate (indicative of early diagnosis) dropped more substantially in 2020q2 in the 61-65 years old age group that was just below the age cut-off of organized screening than in the 66-70 years old age group, and this difference was partially offset in 2021q1. We suggest that policymakers need to motivate the target population (by providing both information and incentives) to catch up on missed screenings.
MeSH term(s)	Aged ; Breast Neoplasms/diagnosis ; COVID-19 ; Early Detection of Cancer ; Female ; Humans ; Mammography ; Mass Screening ; Mastectomy ; Middle Aged ; Pandemics
Language	English
Publishing date	2022-05-25
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	605805-x
ISSN	1872-6054 ; 0168-8510
ISSN (online)	1872-6054
ISSN	0168-8510
DOI	10.1016/j.healthpol.2022.05.013
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Article ; Online: Bone marrow stromal cell-derived hepcidin has antimicrobial and immunomodulatory activities.

Krepuska, Miklós / Mayer, Balázs / Vitale-Cross, Lynn / Myneni, Vamsee D / Boyajian, Michael K / Németh, Krisztián / Szalayova, Ildikó / Cho, Ted / McClain-Caldwell, Ian / Gingerich, Aaron D / Han, Huiling / Westerman, Mark / Rada, Balázs / Mezey, Éva

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3986

Abstract: Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might ... ...

Abstract	Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might also be used as an antimicrobial agent by mammalian BMSCs. In the present study, we show hepcidin expression in both mouse (mBMSC) and human BMSCs (hBMSC). We observed a hBMSC hepcidin-dependent degradation of ferroportin in HEK-293 reporter cells in vitro. In human and mouse bone marrows (BM) we detected hepcidin-positive BMSCs in close proximity to hematopoietic progenitors. The conditioned culture medium of hBMSCs significantly reduced bacterial proliferation that was partially blocked by a hepcidin-neutralizing antibody. Similarly, medium in which hepcidin-deficient (Hamp
MeSH term(s)	Humans ; Mice ; Animals ; Hepcidins/metabolism ; HEK293 Cells ; Mesenchymal Stem Cells ; Anti-Infective Agents/pharmacology ; Inflammation/metabolism ; Bone Marrow Cells ; Mammals
Chemical Substances	Hepcidins ; Anti-Infective Agents
Language	English
Publishing date	2024-02-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54227-1
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Article ; Online: The Potential Use of THP-1, a Monocytic Leukemia Cell Line, to Predict Immune-Suppressive Potency of Human Bone-Marrow Stromal Cells (BMSCs) In Vitro: A Pilot Study.

Ren, Jiaqiang / Szombath, Gergely / Vitale-Cross, Lynn / Stroncek, David F / Robey, Pamela G / Hajdara, Anna / Szalayova, Ildiko / Mayer, Balazs / Martin, Daniel / Mezey, Eva / Nemeth, Krisztian

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might ... ...

Abstract	Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might predict BMSC product efficacy is still unavailable. Below, we show that BMSC donor variability can be monitored by IL-10 production of monocytes/macrophages using THP-1 cells (immortalized monocytic leukemia cells) co-cultured with BMSCs. Using a mixed lymphocyte reaction (MLR) assay, we also compared the ability of the different donor BMSCs to suppress T-cell proliferation, another measure of their immune-suppressive ability. We found that the BMSCs from a donor that induced the most IL-10 production were also the most efficient in suppressing T-cell proliferation. Transcriptome studies showed that the most potent BMSC batch also had higher expression of several known key immunomodulatory molecules such as hepatocyte growth factor (HGF), PDL1, and numerous members of the PGE2 pathway, including PTGS1 and TLR4. Multiplex ELISA experiments revealed higher expression of HGF and IL6 by the most potent BMSC donor. Based on these findings, we propose that THP-1 cells may be used to assess BMSC immunosuppressive activity as a product characterization assay.
MeSH term(s)	Humans ; Pilot Projects ; Bone Marrow ; Interleukin-10 ; Leukemia, Monocytic, Acute ; Cell Line ; Stromal Cells
Chemical Substances	Interleukin-10 (130068-27-8)
Language	English
Publishing date	2023-08-26
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/ijms241713258
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Article ; Online: Targeting Melanoma-Associated Fibroblasts (MAFs) with Activated γδ (Vδ2) T Cells: An In Vitro Cytotoxicity Model.

Hajdara, Anna / Çakır, Uğur / Érsek, Barbara / Silló, Pálma / Széky, Balázs / Barna, Gábor / Faqi, Shaaban / Gyöngy, Miklós / Kárpáti, Sarolta / Németh, Krisztián / Mayer, Balázs

International journal of molecular sciences

2023 Volume 24, Issue 16

Abstract: The tumor microenvironment (TME) has gained considerable scientific attention by playing a role in immunosuppression and tumorigenesis. Besides tumor cells, TME is composed of various other cell types, including cancer-associated fibroblasts (CAFs or ... ...

Abstract	The tumor microenvironment (TME) has gained considerable scientific attention by playing a role in immunosuppression and tumorigenesis. Besides tumor cells, TME is composed of various other cell types, including cancer-associated fibroblasts (CAFs or MAFs when referring to melanoma-derived CAFs) and tumor-infiltrating lymphocytes (TILs), a subpopulation of which is labeled as γδ T cells. Since the current anti-cancer therapies using γδ T cells in various cancers have exhibited mixed treatment responses, to better understand the γδ T cell biology in melanoma, our research group aimed to investigate whether activated γδ T cells are capable of killing MAFs. To answer this question, we set up an in vitro platform using freshly isolated Vδ2-type γδ T cells and cultured MAFs that were biobanked from our melanoma patients. This study proved that the addition of zoledronic acid (1-2.5 µM) to the γδ T cells was necessary to drive MAFs into apoptosis. The MAF cytotoxicity of γδ T cells was further enhanced by using the stimulatory clone 20.1 of anti-BTN3A1 antibody but was reduced when anti-TCR γδ or anti-BTN2A1 antibodies were used. Since the administration of zoledronic acid is safe and tolerable in humans, our results provide further data for future clinical studies on the treatment of melanoma.
MeSH term(s)	Humans ; Zoledronic Acid/pharmacology ; Melanoma ; Fibroblasts ; DiGeorge Syndrome ; Cancer-Associated Fibroblasts ; Tumor Microenvironment
Chemical Substances	Zoledronic Acid (6XC1PAD3KF)
Language	English
Publishing date	2023-08-17
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/ijms241612893
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Article ; Online: Melanoma-associated fibroblasts impair CD8+ T cell function and modify expression of immune checkpoint regulators via increased arginase activity.

Érsek, Barbara / Silló, Pálma / Cakir, Ugur / Molnár, Viktor / Bencsik, András / Mayer, Balázs / Mezey, Eva / Kárpáti, Sarolta / Pós, Zoltán / Németh, Krisztián

Cellular and molecular life sciences : CMLS

2020 Volume 78, Issue 2, Page(s) 661–673

Abstract: This study shows that melanoma-associated fibroblasts (MAFs) suppress cytotoxic T lymphocyte (CTL) activity and reveals a pivotal role played by arginase in this phenomenon. MAFs and normal dermal fibroblasts (DFs) were isolated from surgically resected ... ...

Abstract	This study shows that melanoma-associated fibroblasts (MAFs) suppress cytotoxic T lymphocyte (CTL) activity and reveals a pivotal role played by arginase in this phenomenon. MAFs and normal dermal fibroblasts (DFs) were isolated from surgically resected melanomas and identified as Melan-A-/gp100-/FAP+ cells. CTLs of healthy blood donors were activated in the presence of MAF- and DF-conditioned media (CM). Markers of successful CTL activation, cytotoxic degranulation, killing activity and immune checkpoint regulation were evaluated by flow cytometry, ELISPOT, and redirected killing assays. Soluble mediators responsible for MAF-mediated effects were identified by ELISA, flow cytometry, inhibitor assays, and knock-in experiments. In the presence of MAF-CM, activated/non-naïve CTLs displayed dysregulated ERK1/2 and NF-κB signaling, impeded CD69 and granzyme B production, impaired killing activity, and upregulated expression of the negative immune checkpoint receptors TIGIT and BTLA. Compared to DFs, MAFs displayed increased amounts of VISTA and HVEM, a known ligand of BTLA on T cells, increased L-arginase activity and CXCL12 release. Transgenic arginase over-expression further increased, while selective arginase inhibition neutralized MAF-induced TIGIT and BTLA expression on CTLs. Our data indicate that MAF interfere with intracellular CTL signaling via soluble mediators leading to CTL anergy and modify immune checkpoint receptor availability via L-arginine depletion.
MeSH term(s)	Arginase/genetics ; Arginase/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cancer-Associated Fibroblasts/immunology ; Cancer-Associated Fibroblasts/metabolism ; Cells, Cultured ; Gene Expression Regulation, Neoplastic ; Humans ; Immune Checkpoint Proteins/genetics ; Immune Checkpoint Proteins/immunology ; Lymphocyte Activation ; Melanoma/genetics ; Melanoma/immunology ; Skin Neoplasms/genetics ; Skin Neoplasms/immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism
Chemical Substances	Immune Checkpoint Proteins ; ARG2 protein, human (EC 3.5.3.1) ; Arginase (EC 3.5.3.1)
Language	English
Publishing date	2020-04-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-020-03517-8
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Article ; Online: Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation.

Kárpáti, Sarolta / Sárdy, Miklós / Németh, Krisztián / Mayer, Balázs / Smyth, Neil / Paulsson, Mats / Traupe, Heiko

Experimental dermatology

2018 Volume 27, Issue 8, Page(s) 807–814

Abstract: Transglutaminases (TGs) are structurally and functionally related enzymes that modify the post-translational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, ... ...

Abstract	Transglutaminases (TGs) are structurally and functionally related enzymes that modify the post-translational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, TGs are able to modify the signalling, the function and the fate of cells and extracellular connective tissues. Besides mouse models, human diseases enable us to appreciate the function of various TGs. In this study, skin diseases induced by genetic damages or autoimmune targeting of these enzymes will be discussed. TG1, TG3 and TG5 contribute to the cutaneous barrier and thus to the integrity and function of epidermis. TGM1 mutations related to autosomal recessive ichthyosis subtypes, TGM5 mutations to a mild epidermolysis bullosa phenotype and as novelty TGM3 mutation to uncombable hair syndrome will be discussed. Autoimmunity to TG2, TG3 and TG6 may develop in a few of those genetically determined individuals who lost tolerance to gluten, and manifest as coeliac disease, dermatitis herpetiformis or gluten-dependent neurological symptoms, respectively. These gluten responder diseases commonly occur in combination. In autoimmune diseases, the epitope spreading is remarkable, while in some inherited pathologies, a unique compensation of the lost enzyme function is noted.
MeSH term(s)	Animals ; Apoptosis ; Autoantibodies/immunology ; Celiac Disease/immunology ; Cell Lineage ; Dermatitis Herpetiformis/enzymology ; Dermatitis Herpetiformis/immunology ; Disease Models, Animal ; Epitopes/immunology ; Humans ; Mice ; Mice, Transgenic ; Mutation ; Phenotype ; Signal Transduction ; Skin/enzymology ; Skin/immunology ; Transglutaminases/genetics ; Transglutaminases/physiology
Chemical Substances	Autoantibodies ; Epitopes ; transglutaminase 5 (EC 2.3.2.-) ; Transglutaminases (EC 2.3.2.13)
Language	English
Publishing date	2018-02-26
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1130936-2
ISSN	1600-0625 ; 0906-6705
ISSN (online)	1600-0625
ISSN	0906-6705
DOI	10.1111/exd.13449
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Article ; Online: Visualization of Keratin with Diffuse Reflectance and Autofluorescence Imaging and Nonlinear Optical Microscopy in a Rare Keratinopathic Ichthyosis.

Anker, Pálma / Fésűs, Luca / Kiss, Norbert / Noll, Judit / Becker, Krisztina / Kuroli, Enikő / Mayer, Balázs / Bozsányi, Szabolcs / Lőrincz, Kende / Lihacova, Ilze / Lihachev, Alexey / Lange, Marta / Wikonkál, Norbert / Medvecz, Márta

Sensors (Basel, Switzerland)

2021 Volume 21, Issue 4

Abstract: Keratins are one of the main fluorophores of the skin. Keratinization disorders can lead to alterations in the optical properties of the skin. We set out to investigate a rare form of keratinopathic ichthyosis caused ... ...

Abstract	Keratins are one of the main fluorophores of the skin. Keratinization disorders can lead to alterations in the optical properties of the skin. We set out to investigate a rare form of keratinopathic ichthyosis caused by
MeSH term(s)	Child, Preschool ; Humans ; Hyperkeratosis, Epidermolytic ; Keratins ; Male ; Nonlinear Optical Microscopy ; Optical Imaging ; Skin
Chemical Substances	Keratins (68238-35-7)
Language	English
Publishing date	2021-02-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s21041105
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Article: Mesenchymal-Stromal Cell-like Melanoma-Associated Fibroblasts Increase IL-10 Production by Macrophages in a Cyclooxygenase/Indoleamine 2,3-Dioxygenase-Dependent Manner.

Çakır, Uğur / Hajdara, Anna / Széky, Balázs / Mayer, Balázs / Kárpáti, Sarolta / Mezey, Éva / Silló, Pálma / Szakács, Gergely / Füredi, András / Pós, Zoltán / Érsek, Barbara / Sárdy, Miklós / Németh, Krisztián

Cancers

2021 Volume 13, Issue 24

Abstract: Melanoma-associated fibroblasts (MAFs) are integral parts of melanoma, providing a protective network for melanoma cells. The phenotypical and functional similarities between MAFs and mesenchymal stromal cells (MSCs) prompted us to investigate if, ... ...

Abstract	Melanoma-associated fibroblasts (MAFs) are integral parts of melanoma, providing a protective network for melanoma cells. The phenotypical and functional similarities between MAFs and mesenchymal stromal cells (MSCs) prompted us to investigate if, similarly to MSCs, MAFs are capable of modulating macrophage functions. Using immunohistochemistry, we showed that MAFs and macrophages are in intimate contact within the tumor stroma. We then demonstrated that MAFs indeed are potent inducers of IL-10 production in various macrophage types in vitro, and this process is greatly augmented by the presence of treatment-naïve and chemotherapy-treated melanoma cells. MAFs derived from thick melanomas appear to be more immunosuppressive than those cultured from thin melanomas. The IL-10 increasing effect is mediated, at least in part, by cyclooxygenase and indoleamine 2,3-dioxygenase. Our data indicate that MAF-induced IL-10 production in macrophages may contribute to melanoma aggressiveness, and targeting the cyclooxygenase and indoleamine 2,3-dioxygenase pathways may abolish MAF-macrophage interactions.
Language	English
Publishing date	2021-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13246173
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Article: Report of a Novel ALOX12B Mutation in Self-Improving Collodion Ichthyosis with an Overview of the Genetic Background of the Collodion Baby Phenotype.

Anker, Pálma / Kiss, Norbert / Kocsis, István / Czemmel, Éva / Becker, Krisztina / Zakariás, Sára / Plázár, Dóra / Farkas, Klára / Mayer, Balázs / Nagy, Nikoletta / Széll, Márta / Ács, Nándor / Szalai, Zsuzsanna / Medvecz, Márta

Life (Basel, Switzerland)

2021 Volume 11, Issue 7

Abstract: Collodion baby is a congenital, transient phenotype encountered in approximately 70-90% of autosomal recessive congenital ichthyosis and is an important entity of neonatal erythroderma. The clinical outcome after this severe condition is variable. ... ...

Abstract	Collodion baby is a congenital, transient phenotype encountered in approximately 70-90% of autosomal recessive congenital ichthyosis and is an important entity of neonatal erythroderma. The clinical outcome after this severe condition is variable. Genetic mutations of components of the epidermal lipoxygenase pathway have been implicated in the majority of self-improving collodion ichthyosis (SICI). In SICI, the shedding of the collodion membrane reveals clear skin or only mild residual manifestation of ichthyosis. Here we report the case of a girl born with a severe form of collodion baby phenotype, whose skin almost completely cleared within the first month of life. At the age of 3 years, only mild symptoms of a keratinization disorder remained. However, the severity of erythema and scaling showed mild fluctuations over time. To objectively evaluate the skin changes of the patient, we assessed the ichthyosis severity index. Upon sequencing of the ALOX12B gene, we identified a previously unreported heterozygous nonsense mutation, c.1607G>A (p.Trp536Ter) with the recurrent, heterozygous mutation c.1562A>G (p.Tyr521Cys). Thereby, our findings expand the genotypic spectrum of SICI. In addition, we summarize the spectrum of further genetic diseases that can present at birth as collodion baby, in particular the SICI.
Language	English
Publishing date	2021-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life11070624
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Article: Tumorőssejtek szerepe a melanoma progressziójában és heterogenitásában.

Széky, Balázs / Silló, Pálma / Fábián, Melinda / Mayer, Balázs / Kárpáti, Sarolta / Németh, Krisztián

Orvosi hetilap

2016 Volume 157, Issue 34, Page(s) 1339–1348

Abstract: Over the past decade a rare cell population called cancer stem cells has been identified in both solid tumors and hematologic cancers. These cells are reminiscent of somatic and embryonic stem cells and play a critical role in the initiation and ... ...

Title translation	Role of cancer stem cells in the progression and heterogeneity of melanoma.
Abstract	Over the past decade a rare cell population called cancer stem cells has been identified in both solid tumors and hematologic cancers. These cells are reminiscent of somatic and embryonic stem cells and play a critical role in the initiation and progression of malignancies. As all stem cells, they are able to undergo asymmetric cell division and hence renew themselves and create various other progenies with heterogenous phenotypes. A growing body of literature suggested that stem cell subpopulations contribute significantly to the growth and metastatic properties of melanoma. This review gives a comprehensive overview of the current literature on melanoma stem cells, with a special emphasis on the signaling pathways responsible for the homeostatic growth of melanocytes and the uncontrolled proliferation of melanoma cells. The importance of the local microenvironment are demonstrated through summarizing the role of various cell types, soluble factors and cell adhesion molecules in the progression of melanoma and the creation of treatment resistant cancer cell clones. Last but not least, the models of melanoma progression will be introduced and a variety of cellular markers will be presented that may be used to identify and therapeutically target melanoma. Orv. Hetil., 2016, 157(34), 1339-1348.
MeSH term(s)	Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Humans ; Melanocytes/metabolism ; Melanoma/metabolism ; Melanoma/pathology ; Microphthalmia-Associated Transcription Factor/metabolism ; Neoplasm Metastasis ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology
Chemical Substances	Microphthalmia-Associated Transcription Factor
Language	Hungarian
Publishing date	2016-08
Publishing country	Hungary
Document type	Journal Article ; Review
ZDB-ID	123879-6
ISSN	1788-6120 ; 0030-6002
ISSN (online)	1788-6120
ISSN	0030-6002
DOI	10.1556/650.2016.30487
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