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Article ; Online: Judith Campisi (1948-2024).

Desprez, Pierre-Yves / Kapahi, Pankaj

2024 Volume 24, Issue 5, Page(s) 291

MeSH term(s)	History, 20th Century ; History, 21st Century ; Humans ; Neoplasms/history ; Neoplasms/genetics
Language	English
Publishing date	2024-04-10
Publishing country	England
Document type	Historical Article ; Biography ; Journal Article ; Portrait ; Editorial
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/s41568-024-00687-6
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Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 24: Show issues

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Article: A Fully-Automated Senescence Test (FAST) for the high-throughput quantification of senescence-associated markers.

Neri, Francesco / Takajjart, Selma N / Lerner, Chad A / Desprez, Pierre-Yves / Schilling, Birgit / Campisi, Judith / Gerencser, Akos A

bioRxiv : the preprint server for biology

2024

Abstract: Cellular senescence is a major driver of aging and age-related diseases. Quantification of senescent cells remains challenging due to the lack of senescence-specific markers and generalist, unbiased methodology. Here, we describe the Fully-Automated ... ...

Abstract	Cellular senescence is a major driver of aging and age-related diseases. Quantification of senescent cells remains challenging due to the lack of senescence-specific markers and generalist, unbiased methodology. Here, we describe the Fully-Automated Senescence Test (FAST), an image-based method for the high-throughput, single-cell assessment of senescence in cultured cells. FAST quantifies three of the most widely adopted senescence-associated markers for each cell imaged: senescence-associated β-galactosidase activity (SA-β-Gal) using X-Gal, proliferation arrest via lack of 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and enlarged morphology via increased nuclear area. The presented workflow entails microplate image acquisition, image processing, data analysis, and graphing. Standardization was achieved by i) quantifying colorimetric SA-β-Gal via optical density; ii) implementing staining background controls; iii) automating image acquisition, image processing, and data analysis. In addition to the automated threshold-based scoring, a multivariate machine learning approach is provided. We show that FAST accurately quantifies senescence burden and is agnostic to cell type and microscope setup. Moreover, it effectively mitigates false-positive senescence marker staining, a common issue arising from culturing conditions. Using FAST, we compared X-Gal with fluorescent C
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.22.573123
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Article ; Online: Cell type-dependent modulation of senescence features using Weo electrolyzed water.

Court-Vazquez, Brenda L / Arroyo-Vizcarrondo, Shirley A / Poli, Jonathan A / Nyman, Lara / Halderman, Kelly / Ginter, Anthony / Desprez, Pierre-Yves

Aging

2024 Volume 16, Issue 9, Page(s) 7523–7534

Abstract: Electrolyzed-reduced water has powerful antioxidant properties with constituents that scavenge reactive oxygen species (ROS), which are known to be produced by several intrinsic and extrinsic processes. When there is an imbalance between ROS production ... ...

Abstract	Electrolyzed-reduced water has powerful antioxidant properties with constituents that scavenge reactive oxygen species (ROS), which are known to be produced by several intrinsic and extrinsic processes. When there is an imbalance between ROS production and antioxidant defenses, oxidative stress occurs. Persistent oxidative stress leads to cellular senescence, an important hallmark of aging, and is involved in several age-related conditions and illnesses. This study aims to investigate whether Weo electrolyzed water (WEW) could modulate the phenotype of senescent cells. We compared normal human lung fibroblasts (BJ) and breast cancer cells (T47D) treated with hydrogen peroxide (H
MeSH term(s)	Humans ; Cellular Senescence/drug effects ; Hydrogen Peroxide/pharmacology ; Water ; Oxidative Stress/drug effects ; Cell Line, Tumor ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Senescence-Associated Secretory Phenotype/drug effects ; Reactive Oxygen Species/metabolism ; Female ; Electrolysis
Language	English
Publishing date	2024-04-30
Publishing country	United States
Document type	Journal Article
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.205789
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Article ; Online: Antiretroviral protease inhibitors induce features of cellular senescence that are reversible upon drug removal.

Kuehnemann, Chisaka / Hughes, Jun-Wei B / Desprez, Pierre-Yves / Melov, Simon / Wiley, Christopher D / Campisi, Judith

Aging cell

2022 Volume 22, Issue 1, Page(s) e13750

Abstract: Antiretroviral drugs have dramatically improved the prognosis of HIV-infected patients, with strikingly reduced morbidity and mortality. However, long-term use can be associated with signs of premature aging. Highly active antiretroviral therapy ... ...

Abstract	Antiretroviral drugs have dramatically improved the prognosis of HIV-infected patients, with strikingly reduced morbidity and mortality. However, long-term use can be associated with signs of premature aging. Highly active antiretroviral therapy generally comprises two nucleoside reverse transcriptase inhibitors (NRTIs), with one of three additional antiretroviral drug classes, including protease inhibitors (PIs). One commonality between mitochondrial dysfunction (induced by NRTIs) and defects in lamin A (induced by PIs) is they can cause or accelerate cellular senescence, a state of essentially irreversible growth arrest, and the secretion of many bioactive molecules collectively known as the senescence-associated secretory phenotype (SASP). We hypothesized that senescent cells increase following treatment with certain HIV therapies. We compared the effects of two distinct HIV PIs: ritonavir-boosted atazanavir (ATV/r) and ritonavir-boosted darunavir (DRN/r), used in combination treatments for HIV infection. Upon ATV/r, but not DRN/r, treatment, cells arrested growth, displayed multiple features of senescence, and expressed significantly upregulated levels of many SASP factors. Furthermore, mice receiving sustained ATV/r treatment showed an increase in senescent cells and age-related decline in physiological function. However, removing treatment reversed the features of senescence observed in vivo and cell culture. Given how these features disappeared with drug removal, certain features of senescence may not be prognostic as defined by an irreversible growth arrest. Importantly, for patients that are treated or have been treated with ATV/r, our data suggest that switching to another PI that does not promote premature aging conditions (DRN/r) may improve the associated age-related complications.
MeSH term(s)	Animals ; Mice ; Ritonavir/pharmacology ; Ritonavir/therapeutic use ; HIV Protease Inhibitors/pharmacology ; HIV Protease Inhibitors/therapeutic use ; HIV Infections/drug therapy ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Aging, Premature ; Atazanavir Sulfate/pharmacology ; Atazanavir Sulfate/therapeutic use ; Darunavir/pharmacology ; Darunavir/therapeutic use ; Cellular Senescence
Chemical Substances	Ritonavir (O3J8G9O825) ; HIV Protease Inhibitors ; Anti-HIV Agents ; Atazanavir Sulfate (4MT4VIE29P) ; Darunavir (YO603Y8113)
Language	English
Publishing date	2022-12-20
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13750
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Article ; Online: Gene expression signatures of human senescent corneal and conjunctival epithelial cells.

Kitazawa, Koji / Matsumoto, Akifumi / Numa, Kohsaku / Tomioka, Yasufumi / Zhang, Zhixin A / Yamashita, Yohei / Sotozono, Chie / Desprez, Pierre-Yves / Campisi, Judith

Aging

2023 Volume 15, Issue 18, Page(s) 9238–9249

Abstract: Purpose: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells.: Methods: We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression ...

Abstract	Purpose: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. Methods: We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated. Results: X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation. Conclusion: This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.
MeSH term(s)	Humans ; Transcriptome ; Limbus Corneae/pathology ; Cornea/metabolism ; Epithelial Cells/metabolism ; Conjunctiva
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.205113
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Article ; Online: Senescent characteristics of human corneal endothelial cells upon ultraviolet-A exposure.

Numa, Kohsaku / Patel, Sandip Kumar / Zhang, Zhixin A / Burton, Jordan B / Matsumoto, Akifumi / Hughes, Jun-Wei B / Sotozono, Chie / Schilling, Birgit / Desprez, Pierre-Yves / Campisi, Judith / Kitazawa, Koji

Aging

2024 Volume 16, Issue 8, Page(s) 6673–6693

Abstract: Purpose: The objective of this study was to investigate the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A.: Methods: We assessed cell morphology, senescence-associated β-galactosidase (SA-β- ... ...

Abstract	Purpose: The objective of this study was to investigate the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A. Methods: We assessed cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation and expression of senescence markers ( Results: Cells exposed to 5 J/cm2 of UV-A or to IR exhibited typical senescent phenotypes, including enlargement, increased SA-β-gal activity, decreased cell proliferation and elevated expression of Conclusions: In this study, where senescence was induced by UV-A, a more physiological stress for hCEnCs compared to IR, we determined that UV-A modulated the expression of many genes and proteins typically altered upon IR treatment, a more conventional method of senescence induction, even though UV-A also modulated specific pathways unrelated to IR.
MeSH term(s)	Humans ; Cellular Senescence/radiation effects ; Ultraviolet Rays/adverse effects ; Cell Proliferation/radiation effects ; Endothelial Cells/radiation effects ; Endothelial Cells/metabolism ; Endothelium, Corneal/radiation effects ; Endothelium, Corneal/metabolism ; Cells, Cultured ; Proteomics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; beta-Galactosidase/metabolism ; beta-Galactosidase/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/genetics
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p21 ; beta-Galactosidase (EC 3.2.1.23) ; Cyclin-Dependent Kinase Inhibitor p16
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.205761
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Article ; Online: The Molecular Evolution of Melanoma Distant Metastases.

Bezrookove, Vladimir / Kianian, Sara / McGeever, Lea / Jones, Robyn / Caressi, Chongshan / Nosrati, Mehdi / Kim, Kevin B / Leong, Stanley P / Miller, James R / Desprez, Pierre-Yves / Kashani-Sabet, Mohammed

The Journal of investigative dermatology

2024

Abstract: The evolution of primary melanoma to lymph node and distant metastasis is incompletely understood. We examined the genomic diversity in melanoma progression in matched primary melanomas and lymph node and distant metastases from 17 patients. FISH ... ...

Abstract	The evolution of primary melanoma to lymph node and distant metastasis is incompletely understood. We examined the genomic diversity in melanoma progression in matched primary melanomas and lymph node and distant metastases from 17 patients. FISH analysis revealed cancer cell fractions with monotonic copy number alterations, including PHIP gain and PTEN loss, in the metastatic cascade. By contrast, the cancer cell fraction with copy number alterations for BPTF and MITF was reduced in lymph node metastases but increased in distant metastases. Separately, the cancer cell fraction with NCOA3 copy number alteration was comparable between primary tumors and lymph node metastases yet increased in distant metastases. These results suggest enrichment of the phosphoinositide 3-kinase and MITF pathways in the transition through the metastatic cascade. By contrast, next-generation sequencing analysis did not identify a consistent pattern of changes in variant allele frequency while revealing several intriguing findings, including decreased variant allele frequency in distant metastases and distinct drivers in lymph node versus distant metastases. These results provide evidence that distant melanoma metastasis does not always emanate from lymph node metastasis. These results enhance our understanding of clonal patterns of melanoma metastasis, with possible implications for targeted therapy and metastasis competency.
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2024.03.029
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Article ; Online: Quantitative Proteomic Analysis of the Senescence-Associated Secretory Phenotype by Data-Independent Acquisition.

Neri, Francesco / Basisty, Nathan / Desprez, Pierre-Yves / Campisi, Judith / Schilling, Birgit

Current protocols

2021 Volume 1, Issue 2, Page(s) e32

Abstract: Cellular senescence is a complex stress response that induces an essentially permanent cell cycle arrest and a complex secretory phenotype termed the senescence-associated secretory phenotype (SASP), which drives numerous aging pathologies. ... ...

Abstract	Cellular senescence is a complex stress response that induces an essentially permanent cell cycle arrest and a complex secretory phenotype termed the senescence-associated secretory phenotype (SASP), which drives numerous aging pathologies. Characterization of the SASP can provide insights into aging and disease mechanisms, aging biomarker candidates, and targets for counteracting the deleterious effects of senescent cells. Here we describe a mass spectrometry (MS)-compatible protocol to (1) generate senescent cells using different stimuli, (2) collect conditioned medium containing proteins secreted by senescent cells (i.e., SASP), and (3) prepare the SASP for quantitative proteomic analysis using data-independent acquisition (DIA) MS. © 2021 The Authors. Basic Protocol 1: Generating ionizing radiation-induced senescent and control cells Alternate Protocol 1: Generating doxorubicin-induced senescent and control cells Alternate Protocol 2: Generating oncogenic RAS-induced senescent and control cells Alternate Protocol 3: Generating mitochondrial dysfunction-induced senescent and control cells Alternate Protocol 4: Generating atazanavir/ritonavir-induced senescent and control cells Support Protocol: A multiple-assay approach to confirm the phenotype of senescent cells Basic Protocol 2: Generating conditioned medium from senescent cells cultured in low serum and quiescent control cells Alternate Protocol 5: Generating conditioned medium from senescent cells cultured in complete medium and quiescent control cells Basic Protocol 3: Quantitative proteomic analysis of the SASP.
MeSH term(s)	Cells, Cultured ; Cellular Senescence ; Culture Media, Conditioned ; Phenotype ; Proteomics
Chemical Substances	Culture Media, Conditioned
Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article
ISSN	2691-1299
ISSN (online)	2691-1299
DOI	10.1002/cpz1.32
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Article ; Online: Comprehensive proteomic quantification of bladder stone progression in a cystinuric mouse model using data-independent acquisitions.

Rose, Jacob / Basisty, Nathan / Zee, Tiffany / Wehrfritz, Cameron / Bose, Neelanjan / Desprez, Pierre-Yves / Kapahi, Pankaj / Stoller, Marshall / Schilling, Birgit

PloS one

2022 Volume 17, Issue 6, Page(s) e0250137

Abstract: Cystinuria is one of various disorders that cause biomineralization in the urinary system, including bladder stone formation in humans. It is most prevalent in children and adolescents and more aggressive in males. There is no cure, and only limited ... ...

Abstract	Cystinuria is one of various disorders that cause biomineralization in the urinary system, including bladder stone formation in humans. It is most prevalent in children and adolescents and more aggressive in males. There is no cure, and only limited disease management techniques help to solubilize the stones. Recurrence, even after treatment, occurs frequently. Other than a buildup of cystine, little is known about factors involved in the formation, expansion, and recurrence of these stones. This study sought to define the growth of bladder stones, guided by micro-computed tomography imaging, and to profile dynamic stone proteome changes in a cystinuria mouse model. After bladder stones developed in vivo, they were harvested and separated into four developmental stages (sand, small, medium and large stone), based on their size. Data-dependent and data-independent acquisitions allowed deep profiling of stone proteomics. The proteomic signatures and pathways illustrated major changes as the stones grew. Stones initiate from a small nidus, grow outward, and show major enrichment in ribosomal proteins and factors related to coagulation and platelet degranulation, suggesting a major dysregulation in specific pathways that can be targeted for new therapeutic options.
MeSH term(s)	Animals ; Cystine/metabolism ; Cystinuria ; Male ; Mice ; Proteomics ; Urinary Bladder Calculi/diagnostic imaging ; X-Ray Microtomography
Chemical Substances	Cystine (48TCX9A1VT)
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0250137
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Article ; Online: Automated Dashboards for the Identification of Pathogenic Circulating Tumor DNA Mutations in Longitudinal Blood Draws of Cancer Patients.

Udalov, Aleksandr / Kumar, Lexman / Gaudette, Anna N / Zhang, Ran / Salomao, Joao / Saigal, Sanjay / Nosrati, Mehdi / McAllister, Sean D / Desprez, Pierre-Yves

Methods and protocols

2023 Volume 6, Issue 3

Abstract: The longitudinal monitoring of patient circulating tumor DNA (ctDNA) provides a powerful method for tracking the progression, remission, and recurrence of several types of cancer. Often, clinical and research approaches involve the manual review of ... ...

Abstract	The longitudinal monitoring of patient circulating tumor DNA (ctDNA) provides a powerful method for tracking the progression, remission, and recurrence of several types of cancer. Often, clinical and research approaches involve the manual review of individual liquid biopsy reports after sampling and genomic testing. Here, we describe a process developed to integrate techniques utilized in data science within a cancer research framework. Using data collection, an analysis that classifies genetic cancer mutations as pathogenic, and a patient matching methodology that identifies the same donor within all liquid biopsy reports, the manual work for research personnel is drastically reduced. Automated dashboards provide longitudinal views of patient data for research studies to investigate tumor progression and treatment efficacy via the identification of ctDNA variant allele frequencies over time.
Language	English
Publishing date	2023-05-01
Publishing country	Switzerland
Document type	Journal Article
ISSN	2409-9279
ISSN (online)	2409-9279
DOI	10.3390/mps6030046
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