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  1. Article ; Online: Combination of Genomic Landsscape and 3D Culture Functional Assays Bridges Sarcoma Phenotype to Target and Immunotherapy.

    de Nigris, Filomena / Meo, Concetta / Palinski, Wulf

    Cells

    2023  Volume 12, Issue 17

    Abstract: Genomic-based precision medicine has not only improved tumour therapy but has also shown its weaknesses. Genomic profiling and mutation analysis have identified alterations that play a major role in sarcoma pathogenesis and evolution. However, they have ... ...

    Abstract Genomic-based precision medicine has not only improved tumour therapy but has also shown its weaknesses. Genomic profiling and mutation analysis have identified alterations that play a major role in sarcoma pathogenesis and evolution. However, they have not been sufficient in predicting tumour vulnerability and advancing treatment. The relative rarity of sarcomas and the genetic heterogeneity between subtypes also stand in the way of gaining statistically significant results from clinical trials. Personalized three-dimensional tumour models that reflect the specific histologic subtype are emerging as functional assays to test anticancer drugs, complementing genomic screening. Here, we provide an overview of current target therapy for sarcomas and discuss functional assays based on 3D models that, by recapitulating the molecular pathways and tumour microenvironment, may predict patient response to treatments. This approach opens new avenues to improve precision medicine when genomic and pathway alterations are not sufficient to guide the choice of the most promising treatment. Furthermore, we discuss the aspects of the 3D culture assays that need to be improved, such as the standardisation of growth conditions and the definition of in vitro responses that can be used as a cut-off for clinical implementation.
    MeSH term(s) Humans ; Genomics ; Immunotherapy ; Sarcoma/genetics ; Sarcoma/therapy ; Soft Tissue Neoplasms ; Phenotype ; Tumor Microenvironment/genetics
    Language English
    Publishing date 2023-09-04
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12172204
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Gut Feeling About Developmental Programming Mechanisms: Trimethylamine-N-Oxide May Enhance Atherosclerosis in Offspring of Hypercholesterolemic Mice.

    Palinski, Wulf

    Arteriosclerosis, thrombosis, and vascular biology

    2017  Volume 37, Issue 11, Page(s) 1979–1980

    MeSH term(s) Animals ; Atherosclerosis ; Bile Acids and Salts ; Female ; Hypercholesterolemia ; Methylamines ; Mice ; Oxides ; Pregnancy
    Chemical Substances Bile Acids and Salts ; Methylamines ; Oxides ; trimethylamine (LHH7G8O305)
    Language English
    Publishing date 2017-10-25
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.117.310229
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effect of maternal cardiovascular conditions and risk factors on offspring cardiovascular disease.

    Palinski, Wulf

    Circulation

    2014  Volume 129, Issue 20, Page(s) 2066–2077

    MeSH term(s) Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/physiopathology ; Female ; Fetal Growth Retardation/epidemiology ; Fetal Growth Retardation/physiopathology ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Pregnancy ; Pregnancy Complications, Cardiovascular/epidemiology ; Pregnancy Complications, Cardiovascular/physiopathology ; Prenatal Exposure Delayed Effects/epidemiology ; Prenatal Exposure Delayed Effects/physiopathology ; Risk Factors
    Language English
    Publishing date 2014-05-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.113.001805
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: It takes three to tango: genes complicate the association between birth weight and cardiovascular disease.

    Palinski, Wulf

    Circulation

    2011  Volume 123, Issue 24, Page(s) 2773–2775

    MeSH term(s) Birth Weight/genetics ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Risk Factors
    Language English
    Publishing date 2011-06-21
    Publishing country United States
    Document type Comment ; Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.111.037432
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sodium exposure induces stroke in a genetically susceptible model: new insights into early-life factors modulating adult disease.

    Palinski, Wulf

    Circulation

    2009  Volume 119, Issue 11, Page(s) 1459–1462

    MeSH term(s) Age Factors ; Animals ; Disease Models, Animal ; Humans ; Hypertension/epidemiology ; Hypertension/genetics ; Rats ; Rats, Inbred Dahl ; Risk Factors ; Sodium Chloride, Dietary/pharmacology ; Stroke/epidemiology ; Stroke/genetics
    Chemical Substances Sodium Chloride, Dietary
    Language English
    Publishing date 2009-03-24
    Publishing country United States
    Document type Comment ; Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.109.849554
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Maternal-fetal cholesterol transport in the placenta: good, bad, and target for modulation.

    Palinski, Wulf

    Circulation research

    2009  Volume 104, Issue 5, Page(s) 569–571

    MeSH term(s) ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Sub-Family G, Member 1 ; ATP-Binding Cassette Transporters/metabolism ; Apolipoprotein A-I/metabolism ; Cell Membrane/metabolism ; Cholesterol/metabolism ; DNA-Binding Proteins/metabolism ; Endothelial Cells/metabolism ; Female ; Fetal Blood/metabolism ; Humans ; Hypercholesterolemia/metabolism ; Lipoproteins, HDL3/metabolism ; Liver X Receptors ; Maternal-Fetal Exchange ; Orphan Nuclear Receptors ; Placenta/blood supply ; Pregnancy ; Receptors, Cytoplasmic and Nuclear/metabolism
    Chemical Substances ABCG1 protein, human ; ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Sub-Family G, Member 1 ; Apolipoprotein A-I ; DNA-Binding Proteins ; Lipoproteins, HDL3 ; Liver X Receptors ; Orphan Nuclear Receptors ; Receptors, Cytoplasmic and Nuclear ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2009-03-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.109.194191
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Maternal hypercholesterolaemia during pregnancy affects severity of myocardial infarction in young adults.

    Cacciatore, Francesco / Bruzzese, Giuseppe / Abete, Pasquale / Russo, Giuseppe / Palinski, Wulf / Napoli, Claudio

    European journal of preventive cardiology

    2021  Volume 29, Issue 5, Page(s) 758–765

    Abstract: Aims: Elevated maternal cholesterol during pregnancy (MCP) enhances atherogenesis in childhood, but its possible impact on acute myocardial infarction (AMI) in adults is unknown.: Methods and results: We retrospectively evaluated 310 patients who ... ...

    Abstract Aims: Elevated maternal cholesterol during pregnancy (MCP) enhances atherogenesis in childhood, but its possible impact on acute myocardial infarction (AMI) in adults is unknown.
    Methods and results: We retrospectively evaluated 310 patients who were admitted to hospital and whose MCP data were retrievable. Eighty-nine AMI patients with typical chest pain, transmural infarction Q-waves, elevated creatinine kinase, and 221 controls hospitalized for other reasons were identified. The AMI cohort was classified by MI severity (severe = involving three arteries, left ventricle ejection fraction ≤35, CK-peak >1200 mg/dL, or CK-MB >200 mg/dL). The association of MCP with AMI severity was tested by linear and multiple regression analysis that included conventional cardiovascular risk factors, gender, age, and treatment. Associations of MCP with body mass index (BMI) in patients were assessed by linear correlation. In the AMI cohort, MCP correlated with four measures of AMI severity: number of vessels (β = 0.382, P = 0.001), ejection fraction (β = -0.315, P = 0.003), CK (β = 0.260, P = 0.014), and CK-MB (β = 0.334, P = 0.001), as well as survival time (β = -0.252, P = 0.031). In multivariate analysis of patients stratified by AMI severity, MCP predicted AMI severity independently of age, gender, BMI, and CHD risk factors (odds ratio = 1.382, 95% confidence interval 1.046-1.825; P = 0.023). Survival was affected mainly by AMI severity.
    Conclusions: Maternal cholesterol during pregnancy is associated with adult BMI, atherosclerosis-related risk, and severity of AMI.
    MeSH term(s) Biomarkers ; Creatine Kinase, MB Form ; Female ; Humans ; Hypercholesterolemia ; Myocardial Infarction/diagnosis ; Myocardial Infarction/epidemiology ; Myocardial Infarction/therapy ; Pregnancy ; Retrospective Studies ; Stroke Volume ; Young Adult
    Chemical Substances Biomarkers ; Creatine Kinase, MB Form (EC 2.7.3.2)
    Language English
    Publishing date 2021-10-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2626011-6
    ISSN 2047-4881 ; 2047-4873
    ISSN (online) 2047-4881
    ISSN 2047-4873
    DOI 10.1093/eurjpc/zwab152
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Therapeutic targeting of P2X4 receptor and mitochondrial metabolism in clear cell renal carcinoma models.

    Rupert, Christofer / Dell' Aversana, Carmela / Mosca, Laura / Montanaro, Vittorino / Arcaniolo, Davide / De Sio, Marco / Bilancio, Antonio / Altucci, Lucia / Palinski, Wulf / Pili, Roberto / de Nigris, Filomena

    Journal of experimental & clinical cancer research : CR

    2023  Volume 42, Issue 1, Page(s) 134

    Abstract: Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of renal carcinoma and have correlated mitochondrial ...

    Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of renal carcinoma and have correlated mitochondrial activity with poor survival in a subset of patients. The aim of this study was to determine whether targeting mitochondria-lysosome interaction could be a novel therapeutic approach using patient-derived organoids as avatar for drug response.
    Methods: RNAseq data analysis and immunohistochemistry were used to show overexpression of Purinergic receptor 4 (P2XR4) in clear cell carcinomas. Seahorse experiments, immunofluorescence and fluorescence cell sorting were used to demonstrate that P2XR4 regulates mitochondrial activity and the balance of radical oxygen species. Pharmacological inhibitors and genetic silencing promoted lysosomal damage, calcium overload in mitochondria and cell death via both necrosis and apoptosis. Finally, we established patient-derived organoids and murine xenograft models to investigate the antitumor effect of P2XR4 inhibition using imaging drug screening, viability assay and immunohistochemistry.
    Results: Our data suggest that oxo-phosphorylation is the main source of tumor-derived ATP in a subset of ccRCC cells expressing P2XR4, which exerts a critical impact on tumor energy metabolism and mitochondrial activity. Prolonged mitochondrial failure induced by pharmacological inhibition or P2XR4 silencing was associated with increased oxygen radical species, changes in mitochondrial permeability (i.e., opening of the transition pore complex, dissipation of membrane potential, and calcium overload). Interestingly, higher mitochondrial activity in patient derived organoids was associated with greater sensitivity to P2XR4 inhibition and tumor reduction in a xenograft model.
    Conclusion: Overall, our results suggest that the perturbed balance between lysosomal integrity and mitochondrial activity induced by P2XR4 inhibition may represent a new therapeutic strategy for a subset of patients with renal carcinoma and that individualized organoids may be help to predict drug efficacy.
    MeSH term(s) Humans ; Animals ; Mice ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/metabolism ; Receptors, Purinergic P2X4/metabolism ; Calcium/metabolism ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; Mitochondria/metabolism ; Cell Line, Tumor
    Chemical Substances Receptors, Purinergic P2X4 ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2023-05-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-023-02713-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Aneurysms: leukotrienes weaken aorta from the outside.

    Palinski, Wulf

    Nature medicine

    2004  Volume 10, Issue 9, Page(s) 896–898

    MeSH term(s) 5-Lipoxygenase-Activating Proteins ; Animals ; Aortic Aneurysm, Abdominal/etiology ; Aortic Aneurysm, Abdominal/prevention & control ; Arachidonate 5-Lipoxygenase/metabolism ; Carrier Proteins/metabolism ; Gene Expression Regulation ; Leukotrienes/biosynthesis ; Macrophages/metabolism ; Membrane Proteins/metabolism ; Mice ; Models, Biological
    Chemical Substances 5-Lipoxygenase-Activating Proteins ; Alox5ap protein, mouse ; Carrier Proteins ; Leukotrienes ; Membrane Proteins ; Arachidonate 5-Lipoxygenase (EC 1.13.11.34)
    Language English
    Publishing date 2004-09
    Publishing country United States
    Document type Comment ; News
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm0904-896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: United they go: conjunct regulation of aortic antioxidant enzymes during atherogenesis.

    Palinski, Wulf

    Circulation research

    2003  Volume 93, Issue 3, Page(s) 183–185

    MeSH term(s) Adolescent ; Animals ; Antioxidants/metabolism ; Aorta/enzymology ; Aorta/pathology ; Apolipoproteins E/deficiency ; Apolipoproteins E/genetics ; Arteriosclerosis/enzymology ; Arteriosclerosis/genetics ; Arteriosclerosis/pathology ; Child ; Disease Models, Animal ; Disease Progression ; Enzymes/genetics ; Enzymes/metabolism ; Female ; Gene Expression Regulation ; Humans ; Hypercholesterolemia/metabolism ; Hypercholesterolemia/pathology ; Macrophages/pathology ; Mice ; Mice, Knockout ; Oxidation-Reduction ; Oxidative Stress ; Pregnancy
    Chemical Substances Antioxidants ; Apolipoproteins E ; Enzymes
    Language English
    Publishing date 2003-08-08
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/01.RES.0000087332.75244.42
    Database MEDical Literature Analysis and Retrieval System OnLINE

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