WT1
Wilms tumor protein (WT33)
Publications[править]
The objective of this study was to verify the best mating age of gilts at the first parity. Gilts (n = 86) were divided into nine groups in a factorial arrangement with three Ages (AG1, ≤ 220 d; AG2, 220 to 240 d; AG3, 240 ≤ d), and three weights (WT1 ≤ 140 kg; WT2, 140 to 149 kg; WT3, 150 ≤ kg). A higher body weight gain in AG2 sows during gestation. Sows in AG2 group showed a higher body weight gain at first parity and backfat gain in the parity 2 and 3 during gestation. A greater insulin-like growth factor-1 (IGF-1) was observed in AG1 sows compared with AG3 sows at weaning in the second parity. Sows in WT1 group showed a significant positive effect on the plasma IGF-1 at breeding and weaning time in parity 2. Sows in AG3 group showed a higher plasma leptin at breeding, farrowing, and weaning in the parity 1, and at farrowing in parity 2. Sows in WT3 group showed a higher plasma leptin at breeding, farrowing, and weaning in the parities 1 and 2. Considering the insignificant longevity results, the most efficient time for gilts insemination can be at 220 d when their body weight is 140 kg or lower.
Keywords
- Backfat
- Gilts
- Leptin
- Litter performance
- Longevity
- Mating
Aging is associated with highly reproducible DNA methylation (DNAm) changes, which may contribute to higher prevalence of malignant diseases in the elderly. In this study, we analyzed epigenetic aging signatures in 5,621 DNAm profiles of 25 cancer types from The Cancer Genome Atlas (TCGA). Overall, age-associated DNAm patterns hardly reflect chronological age of cancer patients, but they are coherently modified in a non-stochastic manner, particularly at CpGs that become hypermethylated upon aging in non-malignant tissues. This coordinated regulation in epigenetic aging signatures can therefore be used for aberrant epigenetic age-predictions, which facilitate disease stratification. For example, in acute myeloid leukemia (AML) higher epigenetic age-predictions are associated with increased incidence of mutations in RUNX1, WT1, and IDH2, whereas mutations in TET2, TP53, and PML-PARA translocation are more frequent in younger age-predictions. Furthermore, epigenetic aging signatures correlate with overall survival in several types of cancer (such as lower grade glioma, glioblastoma multiforme, esophageal carcinoma, chromophobe renal cell carcinoma, cutaneous melanoma, lung squamous cell carcinoma, and neuroendocrine neoplasms). In conclusion, age-associated DNAm patterns in cancer are not related to chronological age of the patient, but they are coordinately regulated, particularly at CpGs that become hypermethylated in normal aging. Furthermore, the apparent epigenetic age-predictions correlate with clinical parameters and overall survival in several types of cancer, indicating that regulation of DNAm patterns in age-associated CpGs is relevant for cancer development.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- CpG Islands
- DNA Methylation
- Databases, Genetic
- Epigenesis, Genetic
- Esophageal Neoplasms
- Female
- Humans
- Leukemia, Myeloid, Acute
- Male
- Middle Aged
- Mutation
- Neoplasms
- Prognosis
- Reference Values
The Wilms tumor protein 1 (WT1) transcription factor has been associated in malignant melanoma with cell survival and metastasis, thus emerging as a candidate for targeted therapy. A lysine-arginine rich peptide, WT1-pTj, derived from the ZF domain of WT1 was evaluated as an antitumor agent against A2058 human melanoma cells and B16F10-Nex2 syngeneic murine melanoma. Peptide WT1-pTj quickly penetrated human melanoma cells and induced senescence, recognized by increased SA-β-galactosidase activity, enhanced transcriptional activity of p53, and induction of the cell cycle inhibitors p21 and p27. Moreover, the peptide bound to p53 and competed with WT1 protein for binding to p53. WT1-pTj treatment led to sustained cell growth suppression, abrogation of clonogenicity and G2/M cell cycle arrest. Notably, in vivo studies showed that WT1-pTj inhibited both the metastases and subcutaneous growth of murine melanoma in syngeneic mice, and prolonged the survival of nude mice challenged with human melanoma cells. The 27-amino acid cell-penetrating WT1-derived peptide, depends on C(3) and H(16) for effective antimelanoma activity, inhibits proliferation of WT1-expressing human tumor cell lines, and may have an effective role in the treatment of WT1-expressing malignancies.
Keywords
- C PEP, control peptide
- CL-ELISA, chemiluminescence ELISA
- CPP, cell-penetrating peptide
- Malignant melanoma
- SA-βGal, senescence-associated β-galactosidase
- Senescence
- TMZ, Temozolomide
- WT1, Wilms tumor protein 1
- Wilms tumor 1 (WT1)
- ZF, zinc-finger
- p53
- pTj, Trojan peptide