Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma

Broestl, Lauren; Warrington, Nicole M.; Grandison, Lucia; Abou-Antoun, Tamara; Tung, Olivia; Shenoy, Saraswati; Tallman, Miranda M.; Rhee, Gina; Yang, Wei; Sponagel, Jasmin; Yang, Lihua; Kfoury-Beaumont, Najla; Hill, Charles W. L.; Qanni, Sulaiman A.; Mao, Diane D.; Kim, Albert H.; Stewart, Sheila A.; Venere, Monica; Luo, Jingqin; Rubin, Joshua B.

doi:10.1038/s42003-022-03743-9

Cited by 16 publications

(12 citation statements)

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“…An accompanying analysis of survival data from 3.7 million cases in the SEER database, representing approximately 28% of the cancer population, confirmed that mortality rates are higher for males compared to females [2]. These clinically important sex differences are concordant with described sex differences in cell biology including, response to genotoxic stress [3,4], DNA repair [5,6], mutational burden [7,8], metabolism [9,10], and cell cycle regulation [11][12][13], as well as in systems biology including: immunity [14], metabolism [15,16], tissue repair [17,18], and longevity [19,20]. This suggests that therapies for all cancer patients may be advanced by a realistic translation of sex differences into clinical practice.…”

Section: Introductionmentioning

confidence: 60%

Accounting for sex differences variability in the design of sex-adapted cancer treatments

Yang

Rubin

2023

Preprint

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The significant sex differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. We hypothesized that one barrier to translation is that sex differences in cancer phenotypes resemble sex differences in height: highly overlapping, but distinct, male and female population distributions that vary continuously between female- and male- biased extremes. A consequence of this variance is that sex-specific treatments are rendered unrealistic, and our translational goal should be adaptation of treatment to the unique mix of sex-biased mechanisms that are present in each patient. To develop a tool that could advance this goal, we applied a Bayesian Nearest Neighbor (BNN) analysis to 8370 cancer transcriptomes from 26 different adult and 4 different pediatric cancer types to establish patient-specific Transcriptomic Sex Indices (TSI). TSI precisely partitions an individual patients whole transcriptome into female- and male- biased components such that cancer type, patient sex, and transcriptomics, provide a novel and patient-specific mechanistic identifier that can be used for sex-adapted, precision cancer treatment planning.

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Section: Introductionmentioning

confidence: 60%

Accounting for sex differences variability in the design of sex-adapted cancer treatments

Yang

Rubin

2023

Preprint

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“…The major contributing factor to cell senescence is DNA damage (Durik et al, 2012; Yousefzadeh et al, 2021). From the existing literature, female sex is associated with reduced capacity for DNA repair in different organs and cell types (Broestl et al, 2022; Kfoury et al, 2018; Malorni et al, 2008; Rall‐Scharpf et al, 2021; Sun et al, 2014; Trzeciak et al, 2008), with one exception to this assumption found by Yousefzadeh et al (2020). Walker et al found that age (>55 y/o) has a greater effect on activating DNA damage response and senescence in aged women compared with aged men (Walker et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex‐dependent manner

Noh,

Blasco‐Conesa,

Rahman

et al. 2023

Aging Cell

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Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age‐related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence‐associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived from aged female mice are more susceptible to iron‐induced senescence, compared with CEC from aged males. We found that aged female mice, but not males, showed cognitive deficits when chronically treated with ferric citrate (FC), and their brains and the brain vasculature showed senescence‐associated phenotype. We also found that primary culture of CEC derived from aged female mice, but not male‐derived CEC, exhibited senescence‐associated phenotype when treated with FC. We identified that the transmembrane receptor Robo4 was downregulated in the brain vasculature and in cultured primary CEC derived from aged female mice, compared with those from male mice. We discovered that Robo4 downregulation contributed to enhanced vulnerability to FC‐induced senescence. Thus, our study identifies Robo4 downregulation as a driver of senescence induced by iron overload in primary culture of CEC and a potential risk factor of brain vasculature impairment and brain dysfunction.

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“…Commonly, male fetuses have a bigger morphometric body compared with female fetuses [4]. Cells in male fetuses have higher numbers than in females [5]. The different cells number affected by the size of a muscle, a male fetus has a bigger muscle size.…”

Section: Introductionmentioning

confidence: 99%

The intensity of the magnetic field on different sex of fetus and accuracy of sex detection using gold ring pendulum

et al. 2023

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Objective: This research aims to measure the intensity of magnetic field of different sex of fetuses and the accuracy of pendulum method for the sex detection of cow fetuses. Methods: Twenty-six Madura cows with gestational age of more than 4 months were used in this research. This research is composed of three steps : 1). Measuring the intensity of the magnetic field on the fetus using an Electromagnetic Field Meter (EMF) type 827 which is affixed to the right side of the abdomen 2). Observe the pattern of the gold ring pendulum used for sex detection of cow fetus 3). Measure the accuracy of the pendulum ring gold method. The data were analyzed using descriptive analysis. Results: The result of this research showed that the intensity of the magnetic field of a male fetus is 0.04 µT for a head, 0.07 µT for back, 0.05 µT for abdomen and 0.03 µT for tail. Magnetic field of a female fetus is 0.03 µT for head, 0.05 µT for back, 0.035 µT for abdomen and 0.01 µT for tail. The gold ring pendulum is a unidirectional pattern for detection male sex showed the accuracy of 91.67% and a rotating pattern for female fetuses showed accuracy of 85.71%. The average accuracy of detection using the gold ring pendulum is 88.46%. Conclusions: The conclusion of this research is male fetuses have a magnetic field higher than male fetus.

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Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma

Cited by 16 publications

References 50 publications

Accounting for sex differences variability in the design of sex-adapted cancer treatments

Accounting for sex differences variability in the design of sex-adapted cancer treatments

Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex‐dependent manner

The intensity of the magnetic field on different sex of fetus and accuracy of sex detection using gold ring pendulum

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