Role of Sex in the Therapeutic Targeting of p53 Circuitry

Mancini, Francesca; Giorgini, Ludovica; Teveroni, Emanuela; Pontecorvi, Alfredo; Moretti, Fabiola

doi:10.3389/fonc.2021.698946

Cited by 4 publications

(3 citation statements)

References 113 publications

(142 reference statements)

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“…MDMX could be involved in the reprogramming of fetal macrophages (HC) during preeclampsia and other gestational complications and labor. Drawing from the breast cancer literature [ 72 ], downregulation of placental MDMX in preeclampsia could be linked to estrogen receptor-α [ 73 ] and lower estrogen levels [ 74 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10–8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

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Section: Discussionmentioning

confidence: 99%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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show abstract

“…MDMX could be involved in the reprogramming of fetal macrophages (HC) during preeclampsia and other gestational complications and labor. Drawing from the breast cancer literature 70 , downregulation of placental MDMX in preeclampsia could be linked to estrogen receptor-α 71 and lower estrogen levels 72,73 .…”

Section: And Transmission Electron Microscopy Images In a Study At Tw...mentioning

confidence: 99%

Proteomic studies of human placentas reveal partnerships associated with preeclampsia, diabetes, gravidity, and labor

Ho¹,

Chaput²,

Sinkey³

et al. 2023

Preprint

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VEGFR2 is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX and PICALM. The oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages. MDMX, PICALM, and V1aR were on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before labor. We found select associations between higher MDMX, PICALM, OT-R and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations between PICALM-OT-R (p<2.7x10-8), PICALM-V1aR (p<0.006), and OT-R-V1aR (p<0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

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“…There is accumulating evidence that genes and proteins are differentially expressed between males and females. For example, genomics studies have linked sex with p53 and MDM2/4 mutations [86]. Another study that focuses on understanding why Kaposi sarcoma-associated herpesvirus preferentially infects and causes Kaposi sarcoma in males suggested that the androgen receptor is a functional prerequisite for cell invasion by Kaposi sarcoma-associated herpesvirus [87].…”

Section: Genomicsmentioning

confidence: 99%

Clinical Informatics Approaches to Understand and Address Cancer Disparities

2022

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Objectives: Disparities in cancer incidence and outcomes across race, ethnicity, gender, socioeconomic status, and geography are well-documented, but their etiologies are often poorly understood and multifactorial. Clinical informatics can provide tools to better understand and address these disparities by enabling high-throughput analysis of multiple types of data. Here, we review recent efforts in clinical informatics to study and measure disparities in cancer. Methods: We carried out a narrative review of clinical informatics studies related to cancer disparities and bias published from 2018-2021, with a focus on domains such as real-world data (RWD) analysis, natural language processing (NLP), radiomics, genomics, proteomics, metabolomics, and metagenomics. Results: Clinical informatics studies that investigated cancer disparities across race, ethnicity, gender, and age were identified. Most cancer disparities work within clinical informatics used RWD analysis, NLP, radiomics, and genomics. Emerging applications of clinical informatics to understand cancer disparities, including proteomics, metabolomics, and metagenomics, were less well represented in the literature but are promising future research avenues. Algorithmic bias was identified as an important consideration when developing and implementing cancer clinical informatics techniques, and efforts to address this bias were reviewed. Conclusions: In recent years, clinical informatics has been used to probe a range of data sources to understand cancer disparities across different populations. As informatics tools become integrated into clinical decision-making, attention will need to be paid to ensure that algorithmic bias does not amplify existing disparities. In our increasingly interconnected medical systems, clinical informatics is poised to untap the full potential of multi-platform health data to address cancer disparities.

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Role of Sex in the Therapeutic Targeting of p53 Circuitry

Cited by 4 publications

References 113 publications

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Proteomic studies of human placentas reveal partnerships associated with preeclampsia, diabetes, gravidity, and labor

Clinical Informatics Approaches to Understand and Address Cancer Disparities

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