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Buch ; Online: Microenvironment in Disease and Aging

LaBarge, Mark A. / Curtis Hines, William / Charles Radisky, Derek / Park, Catherine

2020

Schlagwörter	Science: general issues ; Biology, life sciences ; microenvironment ; extracellular matrix ; disease ; cancer ; aging
Umfang	1 electronic resource (201 pages)
Verlag	Frontiers Media SA
Dokumenttyp	Buch ; Online
Anmerkung	English ; Open Access
HBZ-ID	HT021230518
ISBN	9782889634163 ; 2889634167
Datenquelle	ZB MED Katalog Medizin, Gesundheit, Ernährung, Umwelt, Agrar

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Artikel: Multiplex Digital Spatial Profiling in Breast Cancer Research: State-of-the-Art Technologies and Applications across the Translational Science Spectrum.

Rossi, Matilde / Radisky, Derek C

Cancers

2024 Band 16, Heft 9

Abstract: While RNA sequencing and multi-omic approaches have significantly advanced cancer diagnosis and treatment, their limitation in preserving critical spatial information has been a notable drawback. This spatial context is essential for understanding ... ...

Abstract	While RNA sequencing and multi-omic approaches have significantly advanced cancer diagnosis and treatment, their limitation in preserving critical spatial information has been a notable drawback. This spatial context is essential for understanding cellular interactions and tissue dynamics. Multiplex digital spatial profiling (MDSP) technologies overcome this limitation by enabling the simultaneous analysis of transcriptome and proteome data within the intact spatial architecture of tissues. In breast cancer research, MDSP has emerged as a promising tool, revealing complex biological questions related to disease evolution, identifying biomarkers, and discovering drug targets. This review highlights the potential of MDSP to revolutionize clinical applications, ranging from risk assessment and diagnostics to prognostics, patient monitoring, and the customization of treatment strategies, including clinical trial guidance. We discuss the major MDSP techniques, their applications in breast cancer research, and their integration in clinical practice, addressing both their potential and current limitations. Emphasizing the strategic use of MDSP in risk stratification for women with benign breast disease, we also highlight its transformative potential in reshaping the landscape of breast cancer research and treatment.
Sprache	Englisch
Erscheinungsdatum	2024-04-23
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16091615
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Inflammation, Infiltration, and Evasion-Tumor Promotion in the Aging Breast.

Cruz-Reyes, Nicole / Radisky, Derek C

Cancers

2023 Band 15, Heft 6

Abstract: Breast cancer is a significant cause of morbidity and mortality in women, with over two million new cases reported worldwide each year, the majority of which occur in post-menopausal women. Despite advances in early detection and treatment, approximately ...

Abstract	Breast cancer is a significant cause of morbidity and mortality in women, with over two million new cases reported worldwide each year, the majority of which occur in post-menopausal women. Despite advances in early detection and treatment, approximately one-third of patients diagnosed with breast cancer will develop metastatic disease. The pathogenesis and progression of breast cancer are influenced by a variety of biological and social risk factors, including age, ethnicity, pregnancy status, diet, and genomic alterations. Recent advancements in breast cancer research have focused on harnessing the power of the patient's adaptive and innate immune systems for diagnostic and therapeutic purposes. The breast immune microenvironment plays a critical role in regulating tissue homeostasis and resistance to tumorigenesis. In this review, we explore the dynamic changes in the breast immune microenvironment that occur with age, how these changes impact breast cancer development and progression, and how targeted therapeutic interventions that leverage the immune system can be used to improve patient outcomes. Our review emphasizes the importance of understanding the complex interplay between aging, the immune system, and breast cancer, and highlights the potential of immune-based therapies in the fight against this devastating disease.
Sprache	Englisch
Erscheinungsdatum	2023-03-18
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15061836
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Response to Mitr and Pollack.

Wickland, Daniel P / Sherman, Mark E / Radisky, Derek C / Mansfield, Aaron S / Asmann, Yan W

Journal of the National Cancer Institute

2022 Band 114, Heft 12, Seite(n) 1729–1730

Sprache	Englisch
Erscheinungsdatum	2022-06-29
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djac133
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Automated Quantitative Measures of Terminal Duct Lobular Unit Involution and Breast Cancer Risk-Letter.

Degnim, Amy C / Radisky, Derek C / Vachon, Celine M / Sherman, Mark E

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2021 Band 30, Heft 4, Seite(n) 797

Mesh-Begriff(e)	Breast ; Breast Neoplasms/epidemiology ; Female ; Humans ; Mammary Glands, Human ; Risk
Sprache	Englisch
Erscheinungsdatum	2021-03-26
Erscheinungsland	United States
Dokumenttyp	Letter ; Comment
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-20-1694
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: On the role of the microenvironment in mammary gland development and cancer.

Radisky, Derek

Cold Spring Harbor perspectives in biology

2012 Band 4, Heft 9, Seite(n) a013458

Mesh-Begriff(e)	Breast Neoplasms/etiology ; Breast Neoplasms/pathology ; Female ; Humans ; Mammary Glands, Human/growth & development ; Mammary Glands, Human/metabolism ; Mammary Glands, Human/pathology ; Tissue Culture Techniques ; Tumor Microenvironment
Sprache	Englisch
Erscheinungsdatum	2012-09-01
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ISSN	1943-0264
ISSN (online)	1943-0264
DOI	10.1101/cshperspect.a013458
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Engineering of tissue inhibitor of metalloproteinases TIMP-1 for fine discrimination between closely related stromelysins MMP-3 and MMP-10.

Raeeszadeh-Sarmazdeh, Maryam / Coban, Mathew / Mahajan, Shivansh / Hockla, Alexandra / Sankaran, Banumathi / Downey, Gregory P / Radisky, Derek C / Radisky, Evette S

The Journal of biological chemistry

2022 Band 298, Heft 3, Seite(n) 101654

Abstract: Matrix metalloproteinases (MMPs) have long been known as key drivers in the development and progression of diseases, including cancer and neurodegenerative, cardiovascular, and many other inflammatory and degenerative diseases, making them attractive ... ...

Abstract	Matrix metalloproteinases (MMPs) have long been known as key drivers in the development and progression of diseases, including cancer and neurodegenerative, cardiovascular, and many other inflammatory and degenerative diseases, making them attractive potential drug targets. Engineering selective inhibitors based upon tissue inhibitors of metalloproteinases (TIMPs), endogenous human proteins that tightly yet nonspecifically bind to the family of MMPs, represents a promising new avenue for therapeutic development. Here, we used a counter-selective screening strategy for directed evolution of yeast-displayed human TIMP-1 to obtain TIMP-1 variants highly selective for the inhibition of MMP-3 in preference over MMP-10. As MMP-3 and MMP-10 are the most similar MMPs in sequence, structure, and function, our results thus clearly demonstrate the capability for engineering full-length TIMP proteins to be highly selective MMP inhibitors. We show using protein crystal structures and models of MMP-3-selective TIMP-1 variants bound to MMP-3 and counter-target MMP-10 how structural alterations within the N-terminal and C-terminal TIMP-1 domains create new favorable and selective interactions with MMP-3 and disrupt unique interactions with MMP-10. While our MMP-3-selective inhibitors may be of interest for future investigation in diseases where this enzyme drives pathology, our platform and screening strategy can be employed for developing selective inhibitors of additional MMPs implicated as therapeutic targets in disease.
Mesh-Begriff(e)	Humans ; Matrix Metalloproteinase 10/chemistry ; Matrix Metalloproteinase 10/genetics ; Matrix Metalloproteinase 10/metabolism ; Matrix Metalloproteinase 3/chemistry ; Matrix Metalloproteinase 3/genetics ; Matrix Metalloproteinase 3/metabolism ; Protein Engineering ; Tissue Inhibitor of Metalloproteinase-1/chemistry ; Tissue Inhibitor of Metalloproteinase-1/genetics ; Tissue Inhibitor of Metalloproteinase-1/metabolism
Chemische Substanzen	TIMP1 protein, human ; Tissue Inhibitor of Metalloproteinase-1 ; MMP3 protein, human (EC 3.4.24.17) ; Matrix Metalloproteinase 3 (EC 3.4.24.17) ; MMP10 protein, human (EC 3.4.24.22) ; Matrix Metalloproteinase 10 (EC 3.4.24.22)
Sprache	Englisch
Erscheinungsdatum	2022-01-29
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2022.101654
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Activity-based protein profiling reveals active serine proteases that drive malignancy of human ovarian clear cell carcinoma.

Mehner, Christine / Hockla, Alexandra / Coban, Mathew / Madden, Benjamin / Estrada, Rosendo / Radisky, Derek C / Radisky, Evette S

The Journal of biological chemistry

2022 Band 298, Heft 8, Seite(n) 102146

Abstract: Ovarian clear cell carcinoma (OCCC) is an understudied poor prognosis subtype of ovarian cancer lacking in effective targeted therapies. Efforts to define molecular drivers of OCCC malignancy may lead to new therapeutic targets and approaches. Among ... ...

Abstract	Ovarian clear cell carcinoma (OCCC) is an understudied poor prognosis subtype of ovarian cancer lacking in effective targeted therapies. Efforts to define molecular drivers of OCCC malignancy may lead to new therapeutic targets and approaches. Among potential targets are secreted proteases, enzymes which in many cancers serve as key drivers of malignant progression. Here, we found that inhibitors of trypsin-like serine proteases suppressed malignant phenotypes of OCCC cell lines. To identify the proteases responsible for malignancy in OCCC, we employed activity-based protein profiling to directly analyze enzyme activity. We developed an activity-based probe featuring an arginine diphenylphosphonate warhead to detect active serine proteases of trypsin-like specificity and a biotin handle to facilitate affinity purification of labeled proteases. Using this probe, we identified active trypsin-like serine proteases within the complex proteomes secreted by OCCC cell lines, including two proteases in common, tissue plasminogen activator and urokinase-type plasminogen activator. Further interrogation of these proteases showed that both were involved in cancer cell invasion and proliferation of OCCC cells and were also detected in in vivo models of OCCC. We conclude the detection of tissue plasminogen activator and urokinase-type plasminogen activator as catalytically active proteases and significant drivers of the malignant phenotype may point to these enzymes as targets for new therapeutic strategies in OCCC. Our activity-based probe and profiling methodology will also serve as a valuable tool for detection of active trypsin-like serine proteases in models of other cancers and other diseases.
Mesh-Begriff(e)	Adenocarcinoma, Clear Cell/enzymology ; Adenocarcinoma, Clear Cell/pathology ; Female ; Humans ; Ovarian Neoplasms/enzymology ; Ovarian Neoplasms/pathology ; Serine Proteases/metabolism ; Tissue Plasminogen Activator/metabolism ; Trypsin ; Urokinase-Type Plasminogen Activator/metabolism
Chemische Substanzen	Serine Proteases (EC 3.4.-) ; Trypsin (EC 3.4.21.4) ; Tissue Plasminogen Activator (EC 3.4.21.68) ; Urokinase-Type Plasminogen Activator (EC 3.4.21.73)
Sprache	Englisch
Erscheinungsdatum	2022-06-16
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2022.102146
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Matrix metalloproteinases as breast cancer drivers and therapeutic targets.

Radisky, Evette S / Radisky, Derek C

Frontiers in bioscience (Landmark edition)

2015 Band 20, Heft 7, Seite(n) 1144–1163

Abstract: Members of the matrix metalloproteinase (MMP) family have been identified as poor prognosis markers for breast cancer patients and as drivers of many facets of the tumor phenotype in experimental models. Early enthusiasm for MMPs as therapeutic targets ... ...

Abstract	Members of the matrix metalloproteinase (MMP) family have been identified as poor prognosis markers for breast cancer patients and as drivers of many facets of the tumor phenotype in experimental models. Early enthusiasm for MMPs as therapeutic targets was tempered following disappointing clinical trials that utilized broad spectrum, small molecule catalytic site inhibitors. However, subsequent research has continued to define key roles for MMPs as breast cancer promoters, to elucidate the complex roles that that these proteins play in breast cancer development and progression, and to identify how these roles are linked to specific and unique biochemical features of individual members of the MMP family. Here, we provide an overview of the structural features of the MMPs, then discuss clinical studies identifying which MMP family members are linked with breast cancer development and new experimental studies that reveal how these specific MMPs may play unique roles in the breast cancer microenvironment. We conclude with a discussion of the most promising avenues for development of therapeutic agents capable of targeting the tumor-promoting properties of MMPs.
Mesh-Begriff(e)	Apoptosis ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Proliferation ; Disease Progression ; Female ; Humans ; Matrix Metalloproteinases/chemistry ; Matrix Metalloproteinases/genetics ; Matrix Metalloproteinases/metabolism ; Matrix Metalloproteinases/physiology ; Models, Molecular ; Neoplasm Invasiveness ; Prognosis ; Protein Structure, Tertiary ; Tumor Microenvironment
Chemische Substanzen	Biomarkers, Tumor ; Matrix Metalloproteinases (EC 3.4.24.-)
Sprache	Englisch
Erscheinungsdatum	2015-06-01
Erscheinungsland	Singapore
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2704569-9
ISSN	2768-6698 ; 1093-9946
ISSN (online)	2768-6698
ISSN	1093-9946
DOI	10.2741/4364
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Lower Exome Sequencing Coverage of Ancestrally African Patients in The Cancer Genome Atlas.

Wickland, Daniel P / Sherman, Mark E / Radisky, Derek C / Mansfield, Aaron S / Asmann, Yan W

Journal of the National Cancer Institute

2022 Band 114, Heft 8, Seite(n) 1192–1199

Abstract: Background: In the United States, cancer disproportionately impacts Black and African American individuals. Identifying genetic factors underlying cancer disparities has been an important research focus and requires data that are equitable in both ... ...

Abstract	Background: In the United States, cancer disproportionately impacts Black and African American individuals. Identifying genetic factors underlying cancer disparities has been an important research focus and requires data that are equitable in both quantity and quality across racial groups. It is widely recognized that DNA databases quantitatively underrepresent minorities. However, the differences in data quality between racial groups have not been well studied. Methods: We compared the qualities of germline and tumor exomes between ancestrally African and European patients in The Cancer Genome Atlas of 7 cancers with at least 50 self-reported Black patients in the context of sequencing depth, tumor purity, and qualities of germline variants and somatic mutations. Results: Germline and tumor exomes from ancestrally African patients were sequenced at statistically significantly lower depth in 6 out of the 7 cancers. For 3 cancers, most ancestrally European exomes were sequenced in early sample batches at higher depth, whereas ancestrally African exomes were concentrated in later batches and sequenced at much lower depth. For the other 3 cancers, the reasons of lower sequencing coverage of ancestrally African exomes remain unknown. Furthermore, even when the sequencing depths were comparable, African exomes had disproportionally higher percentages of positions with insufficient coverage, likely because of the known European bias in the human reference genome that impacted exome capture kit design. Conclusions: Overall and positional lower sequencing depths of ancestrally African exomes in The Cancer Genome Atlas led to underdetection and lower quality of variants, highlighting the need to consider epidemiological factors for future genomics studies.
Mesh-Begriff(e)	Exome/genetics ; Genome, Human ; Genomics ; Humans ; Neoplasms/genetics ; United States/epidemiology ; Whole Exome Sequencing
Sprache	Englisch
Erscheinungsdatum	2022-03-17
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djac054
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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