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Objective To investigate the relationship between expression levels of epidermal growth factor receptor (EGFR), proliferation marker protein Ki-67 (Ki-67), P53 and circulating tumor cell (CTC) and the prognosis of triple negative breast cancer. Methods A total of 95 patients with triple negative breast cancer were selected. The expression levels of EGFR, Ki-67 and P53 in pathological tissue specimens were detected by immunohistochemistry. All patients underwent 8 cycles of chemotherapy, and the expression of CTC was detected before and after chemotherapy by isolation epithelial tumor cells (ISET). The relationship between CTC expression before and after chemotherapy and efficacy of chemotherapy was analyzed. The correlation between CTC and expression levels of EGFR, Ki-67 and P53 was analyzed. Patients were followed up for progression free survival (PFS). Risk factors of progression for triple negative breast cancer were analyzed by COX regression. Results The positive detection rates of EGFR, Ki-67 and P53 were 44.21% (42/95), 63.16% (60/95) and 56.84% (54/95). The positive detection rate of CTC was lower in patients after chemotherapy than that before chemotherapy (14.74% vs. 61.05%, P＜0.05). The efficacy of chemotherapy was negatively correlated with the positive expression of CTC after chemotherapy (P＜0.001). COX regression analysis found that clinical stage Ⅲ, positive EGFR and CTC after chemotherapy were independent risk factors of progression of triple negatively breast cancer (P＜0.05). PFS of patients at clinical stage Ⅰ, stage Ⅱ, and stage Ⅲ decreased in order (P＜0.05). PFS of EGFR positive patients was shorter than that of EGFR negative patients (P＜0.05). PFS of CTC positive patients after chemotherapy was shorter than that of CTC negative patients after chemotherapy (P＜0.05). Conclusion The positive expression of EGFR before chemotherapy and the positive expression of CTC after chemotherapy are related to the poor survival prognosis of patients with triple negative breast cancer. The lower the positive detection rate of CTC after chemotherapy, the better the efficacy of chemotherapy. [ABSTRACT FROM AUTHOR]

Objective(s): It is worthwhile to note that, some probiotics such as Lactobacilli and Bifidobacteria isolated from dairy products have significant therapeutic effects against cancer cells. Here, we evaluated anti-proliferation and the apoptotic effects of isolated Lactobacillus fermentum Ab.RS22 from traditional dairy products on the HeLa cervical cancer cells in vitro. Materials and Methods: The viability of treated HeLa cells with supernatant of Lactobacillus in 0.5, 0.75, 1, 1.5, and 2 ng/ml concentrations, and IC50 values were detected by tetrazolium bromide. The L. fermentum Ab.RS22-induced cell death by flow cytometry was confirmed through evaluation of the expression of caspase-3, P53, PTEN, and AKT genes by quantitative reverse transcriptionpolymerase chain reactions (qRT-PCR). Results: Most cytotoxicity effects of Lactobacillus on HeLa cells were detected in 2 ng/ml at 24 hr (P<0.01); also, the IC50 value was measured as 1.5 ng/ml. The findings of the flow cytometry assay showed that L. fermentum Ab.RS22 in 1.5 ng/ml concentration at 24 hr increased the percentage of both apoptosis and necrosis cells. Lactobacillus-induced cell death was verified through results of Real-time PCR; where expression of caspase-3, P53, and PTEN genes was increased (P<0.01), and also expression of AKT gene (anti-apoptotic) was decreased (P<0.05). Conclusion: Our findings showed that L. fermentum Ab.RS22 could dose-dependently inhibit the proliferation of the HeLa cells. Its apoptotic effect was confirmed via modulating PTEN/p53/Akt gene expression and activation of the caspase-3 mediated apoptosis pathway. Therefore, L. fermentum Ab.RS22 can be considered a valuable anticancer candidate against cervical cancer progression in subsequent studies. [ABSTRACT FROM AUTHOR]

Background: C-phycocyanin, a biliprotein from Spirulina platensis, is a future candidate for cancer management. This agent is originated from edible blue-green algae, and numerous in vivo and in vitro research have reported on its anti-cancer properties. The effects of Cphycocyanin have been investigated on caspases 3, 8, 9, and p53 pathways in the human colorectal adenocarcinoma cell line (HT-29) and human umbilical vein endothelial cells (HUVECs). Methods: In the current study, we investigated the effect of C-phycocyanin on caspase 3, 8, 9, and p53-mediated apoptosis pathways in two cell lines (HT-29 & HUVEC), using quantitative real-time PCR and flow cytometry. The cytotoxicity of phycocyanin on HT-29 cells was compared with HUVEC normal cells via colorimetric assays. Results: Based on our findings at molecular level, the expression of caspases 3, 8, 9, and p53 genes were increased in colorectal cancer cells treated with C-phycocyanin. The results were confirmed by an increase in the number of colorectal cancer cells in the early and late stages of apoptosis as compared to the control, untreated cells. In addition, the results of colorimetric assay showed that C-phycocyanin has no cytotoxic effects on normal HUVECs cells. Conclusions: Based on our experimental data, it is evident that C-phycocyanin has measurable effects on cell apoptosis. Since tumorigenesis is halted by apoptosis, C-phycocyanin can be a hopeful candidate for the treatment of human colorectal cancer in the future. [ABSTRACT FROM AUTHOR]

Background: Autoantibody detection is a promising approach to cancer screening. Serum p53 antibodies have been time tested in various cancers, including oral squamous cell carcinoma (OSCC). This study is aimed to detect and determine the level of p53 autoantibodies (p53-AAbs) in saliva. The association of clinicopathological features among patients with and without OSCC was also explored as a novel method for the detection of autoantibodies. Methods: One hundred preoperative saliva samples from patients with histologically confirmed OSCC and a hundred from normal healthy individuals were collected. Anti p53 detection kit assessed levels of salivary p53-AAbs. The cut-off value was 1.3 U/mL by Enzyme-linked immunosorbent assay (ELISA). The p53-AAb levels were expressed in terms of the median and interquartile range (IQR). Fischer's exact test and Chi-square test were used to determine the association with clinicopathological features among patients with OSCC and healthy controls with tobacco consumption habits. Results: Median level of p53-AAb is 0.234 U/mL (IQR 0.18-0.37U/mL) in healthy controls and 0.285U/mL (IQR 0.16-0.58U/mL) in OSCC. p53-AAbs was positive in 15% of 100 patients with OSCC, which was statistically higher (P < 0.001) among OSCC, and controls were negative for p53-AAb. No significant correlation of p53-AAbs with the patient's age, gender, site, clinical staging (TNM), and pathologic grade was observed. However, a significant association was seen between the node involvement and salivary p53-AAbs. Conclusion: Salivary p53-AAb positivity was seen in a higher proportion in OSCC patients than in healthy controls with tobacco consumption, and the levels did differ significantly among OSCC and healthy controls. [ABSTRACT FROM AUTHOR]

The p53 protein is a transcriptional regulatory factor and many of its functions require that it forms a tetrameric structure. Although the tetramerization domain of mammalian p53 proteins (p53TD) share significant sequence similarities, it was recently shown that the tree shrew p53TD is considerably more thermostable than the human p53TD. To determine whether other mammalian species display differences in this domain, we used biophysical, functional, and structural studies to compare the properties of the p53TDs from six mammalian model organisms (human, tree shrew, guinea pig, Chinese hamster, sheep, and opossum). The results indicate that the p53TD from the opossum and tree shrew are significantly more stable than the human p53TD, and there is a correlation between the thermostability of the p53TDs and their ability to activate transcription. Structural analysis of the tree shrew and opossum p53TDs indicated that amino acid substitutions within two distinct regions of their p53TDs can dramatically alter hydrophobic packing of the tetramer, and in particular substitutions at positions corresponding to F341 and Q354 of the human p53TD. Together, the results suggest that subtle changes in the sequence of the p53TD can dramatically alter the stability, and potentially lead to important changes in the functional activity, of the p53 protein. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of taurine (Tau) on the proliferation, apoptosis and migration of pancreatic cancer ductal cells. Methods BxPC-3 and PANC-1 cells were cultured in vitro and pretreated with different concentrations of Tau (0, 10, 20, 40, 80, 160 mmol/L). Cell counting kit-8 (CCK-8), cell scratch assay and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method were used to observe the effect of Tau on the proliferation, migration and apoptosis of BxPC-3 and PANC-1 cells. Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were used to detect the effect of Tau on mRNA and protein expression of relevant apoptosis and cell cycle molecules in BxPC-3 and PANC-1 cells. Results Tau significantly inhibited the proliferation and migration activities of BxPC-3 and PANC-1, and Tau could promote the apoptosis of BxPC-3 and PANC-1 cells. Compared with the control group, expression levels of P53, P21 and BAX in BxPC-3 cells treated with Tau showed a significant upward trend, while the expression of PCNA was significantly decreased. The expression levels of Bcl-2, PCNA, CyclinA2, CyclinB1, CyclinE, CDK1, CDK2, CDK4 and CDK6 in PANC-1 cells were significantly lower than those in the normal control group, while the expression levels of P53 and P21 showed an upward trend. Conclusion Tau can inhibit the proliferation and migration activity of BxPC-3 and PANC-1 pancreatic cancer cells, and promote cell apoptosis, possibly by affecting related apoptosis genes and cyclins. [ABSTRACT FROM AUTHOR]

Background & Objective: Some of the patients with myelodysplastic syndrome (MDS) are categorized as good prognosis based on the Revised International Prognostic Scoring System (IPSS-R). However, these patients may have poor clinical outcomes. It seems that the current diagnostic tools and IPSS-R cannot consider genetic factors for determining the prognosis of MDS patients. Methods: This cross-sectional study included all adult MDS patients of both genders who were admitted from March 2015 to March 2020 to the Hematology wards of two educational tertiary hospitals in Iran (Namazi and Faghihi, affiliated with Shiraz University of medical sciences). Study data included relevant retrospective data from medical records and the results of immunohistochemical p53 staining on bone marrow biopsies. Results: Of the 84 patients, 65 (77.4%) showed p53 expression in bone marrow. They had shorter median survival than those without p53 expression. Considering both variables of P53 IHC results and IPSS-R score, the patients who died with low-risk IPSS-R score presented high p53 expression. Conclusion: This study shows that the investigation of p53 expression by IHC at the time of diagnosis is a valuable indicator of survival rate in MDS patients. These data suggest that the immunohistochemical analysis of p53 can be a prognostic tool for MDS and should be used as an adjunct test to make decisions on the best therapeutic choice. [ABSTRACT FROM AUTHOR]

Objective To explore the correlation between the loss of expression of alpha thalassemia with mental retardation syndrome gene (ATRX) and over expression of P53 in patients with glioma and to analyze the clinical significance of the two gene expression and multi-factors in the diagnosis and prognosis of glioma. Method The clinical data of 92 patients were collected, including 30 patients with astrocytoma of grade Ⅱ/Ⅲ (WHO), 50 with oligodendroglioma of grade Ⅱ/Ⅲ (WHO) and 12 with glioblastoma of grade Ⅳ (WHO). The Chi-square test was applied to analyze the relationship between the two gene expression and different pathological types of glioma. The Spearman’s rank correlation analysis was used to analyze the correlation between their different expression. Kaplan-Meier survival curve was designed to investigate the clinical value of their different expression in prognosis of patients with glioma. The other contributing factors were analyzed in the multivariate Cox regression analysis. Results There was a correlation between the different expression of ATRX and P53 and the pathological types of glioma (P＜0.05). The correlation analysis showed that the loss of expression of ATRX and over expression of P53 in glioma were negative correlated (r=0.426,P＜0.01). The multivariate analysis showed that the age over 60 years old, grade Ⅲ/Ⅳ (WHO), preoperative KPS scores below 60 points, lack of postoperative radiotherapy and chemotherapy, and lost expression of the ATRX were independently risk factors for poor prognosis. Conclusion In patients with glioma, the loss of expression of ATRX and over expression of P53 were closely related to one another, and they together with other clinical factors can better evaluate the prognosis of glioma patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common type of liver cancer in China, and the development and progression of HCC is a complex pathological process. As a new way of cell death, ferroptosis has huge potential in the treatment of HCC. This article introduces the mechanism of action of the tumor suppressor p53 in regulating ferroptosis and briefly describes its role in the development and progression of HCC. The tumor suppressor p53 can promote or inhibit ferroptosis by affecting solute carrier family 7 member 11, spermidine/spermine N1-acety-ltransferase 1, glutaminase 2, dipeptidyl peptidase 4, and cyclin-dependent kinase inhibitor 1A, which in turn affects the progression of HCC. The treatment of HCC by regulating the ferroptosis pathway has great application prospects. [ABSTRACT FROM AUTHOR]

The article presents the discussion on evaluating the two most used classification systems for OED. Topics include main factors involved in the progression of OPMD to cancer being the presence of oral epithelial dysplasia (OED); and increasing nuclear–cytoplasmic ratio, irregular epithelial stratification, increasing number and size of nucleoli, keratin pearls within rete ridges.

Background and Objectives: Breast cancer is the second leading cause of death and one of the most common malignancies among women in the world. The aim of this study was to investigate the preventive effects of postbiotic consisting of sonicated Bifidobacterium bifidum cells on triple negative breast cancer. Materials and Methods: Thirty-six female BALB/c mice aged 5-7 weeks were randomly divided into 3 groups (n=12): Ctrl-, healthy mice; Ctrl+, mice with breast cancer with no treatment; and Postbiotic, mice with orally gavage postbiotic before and after 4T1 cell line transplantation. Cancer progress and the effects of postbiotic were assayed by histological, immunohistochemical and gene expression quantification. Results: The histological results showed that administration postbiotic consisting of B. bifidum significantly decreased carcinogenesis in terms of tumor incidence, multiplicity and volume. The tumor progress was suppressed by oral intake of B. bifidum as showed by p53 and Ki-67 expression. Furthermore, Oral intake of postbiotic resulted in extended survival of mice and inhibited sever weigh loss. Conclusion: Pretreatment with sonication killed B. bifidum, as a postbiotic, inhibited breast cancer progress and malignancy. [ABSTRACT FROM AUTHOR]

Objectives: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up.We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1.From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1–74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up.This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS.Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Materials and methods: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up.We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1.From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1–74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up.This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS.Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Results: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up.We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1.From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1–74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up.This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS.Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Conclusion: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up.We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1.From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1–74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up.This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS.Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Clinical relevance statement: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up.We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1.From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1–74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up.This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS.Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Key Points: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up.We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1.From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1–74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up.This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS.Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Graphical Abstract: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up.We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1.From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1–74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up.This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS.Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce.Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%.Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients. [ABSTRACT FROM AUTHOR]

Objective: Challenging differential diagnosis Background: Clonal hematopoiesis is the production of a specific single clonal type of cell in the blood and is often found in cancer genomic profiling tests. When the clone carries a pathogenic variant, it may be important to differentiate between somatic or germline origin. The variant in the blood that has a lower minor allele frequency could reflect heterozygous germline origin, somatic mosaicism, and clonal hematopoiesis. It is important to evaluate suspected variants to determine the course of treatment and follow-up of the patient, depending on the patient's medical condition and family situation. Case Report: We report a 57-year-old Japanese man with gastric cancer who underwent a cancer genomic profiling test search- ing for therapeutic agents. The profiling test detected a variant, TP53 c.559+2T>G minor allele frequencies of 9% (168/1865) in tumor tissue and 29.1% (58/199) in paired blood. Since the TP53 variant has the possibility of Li-Fraumeni syndrome, ancillary testing was performed using fingernails, buccal swab, and blood specimens. The genomic analysis revealed no TP53 variant in his fingernails. The patient had previously received platinum-based chemotherapies, suggesting that the variant reflected treatment-induced clonal hematopoiesis. Conclusions: Identifying clonal hematopoiesis when performing genomic profiling tests for patients with cancer is important. Examining multiple tissues to determine whether a variant arises from clonal hematopoiesis or is of germline origin can provide more accurate genetic information and improve patient follow-up care. [ABSTRACT FROM AUTHOR]

Actinic cheilitis (AC) is part of a spectral disease of keratinocyte carcinomas considered by some authors an early stage of in situ squamous cell carcinoma. Treatment options for AC can be lesion and field-directed therapies. Ingenol mebutate (IM) induces rapid and direct cell death and immune responses being able to destruct dysplastic cells. This study enrolled patients with AC to receive IM gel 0.015% for self-application on the lower lip for 3 consecutive days. A biopsy was performed before and after treatment for histopathological and immunohistochemical evaluation. Local skin reactions (LSR) were evaluated. The level of significance considered was 5%. Fourteen patients were enrolled. All LSR had a complete resolution for up to 2 weeks. The most common adverse events were burning sensation, angular cheilitis, and pain. There was an improvement of more than 80% in patients' subjective evaluation. There was no statistically significant histopathological response since all patients remained with mild dysplasia. No reduction in the P53 expression was observed in the current study. Despite being a safe therapeutic method, the absence of histopathological or immunohistochemical response suggests that clinical improvement may not be accompanied by histopathological cure for AC treated with IM. [ABSTRACT FROM AUTHOR]

Objective: To assess the immunohistochemical expression of p53 in tissue samples of oral squamous cell carcinoma (OSCC), oral epithelial precursor lesions, and normal oral mucosa. Material & Methods: A comparative cross-sectional study was jointly conducted at the Departments of Pathology and Oral and Maxillofacial Surgery of various medical and dental institutes of the country from April 2016 to March 2017. A total of 180 subjects were included in the study. Oral tissue specimens were collected for laboratory investigations after obtaining written consent from all subjects. p53 was assessed using immunohistochemistry in tissue samples of 60 cases of OSCC, 60 cases of epithelial precursor lesions, and normal oral mucosal samples of 60 healthy individuals. Data were recorded, evaluated, and analyzed by SPSS-20. Results: p53 protein expression was noted in 85% OSCC and 73% oral epithelial precursor lesions. Among healthy individuals, one subject showed p53 immunoreactivity in the normal oral mucosa. Conclusion: Raised p53 overexpression in OSCC and oral precursor lesions, compared to normal oral mucosa make it a probable candidate for a potential predictive biomarker in oral premalignancy and malignancy. [ABSTRACT FROM AUTHOR]

Considering the importance of lymphoma and its prevalence in communities as well as its relationship with genetic factors (P53 & MDM2) as well as contradictory results about the possible role of deletion / insertion of polymorphisms in different types of cancer. The aim of this study was to investigate the deletion / insertion of 40 bp of mdm2 polymorphism and 16-bp of p53 polymorphism in patients with lymphoma. In this casecontrol study, 152 non-Hodgkin's lymphoma patients and 155 healthy individuals were selected by convenience sampling method. MDM2 and P53 polymorphisms were examined by PCR. SPSS V22 software was used to interpret the results. The results of the study showed that rs3730485 species was associated with the risk of lymphoma. The Ins / Del and Del / Del genotypes reduce the risk of lymphoma compared to the Ins / Ins genotype (OR = 0.41,95% CI = 0.25-0.65 P <0.001 and OR = 0.33.95% CI = 0.12). 0.96, P = 0.035 In relation to Ins / Del + Del / Del and Ins / Del, the results also showed that they reduce the risk of lymphoma (OR = 0.40,95% CI = 0.25-0.63, P <0.001). Results indicated that Ins / Del, Del / Del, Ins / Del + Del / Del and D alleles genotypes had a statistically significant relationship with lymphoma risk. Due to the fact that the OR genotypes of this site are less than one step away, it is a protective factor for lymphoma, so that these alleles and the mentioned genotype reduce the risk of lymphoma. [ABSTRACT FROM AUTHOR]

Disruption of circadian rhythms increases the risk of several types of cancer. Mammalian cryptochromes (CRY1 and CRY2) are circadian transcriptional repressors that are related to DNA-repair enzymes. While CRYs lack DNA-repair activity, they modulate the transcriptional response to DNA damage, and CRY2 can promote SKP1 cullin 1-F-box (SCF)FBXL3-mediated ubiquitination of c-MYC and other targets. Here, we characterize five mutations in CRY2 observed in human cancers in The Cancer Genome Atlas. We demonstrate that two orthologous mutations of mouse CRY2 (D325H and S510L) accelerate the growth of primary mouse fibroblasts expressing high levels of c-MYC. Neither mutant affects steady-state levels of overexpressed c-MYC, and they have divergent impacts on circadian rhythms and on the ability of CRY2 to interact with SCFFBXL3. Unexpectedly, stable expression of either CRY2 D325H or of CRY2 S510L robustly suppresses P53 target-gene expression, suggesting that this may be a primary mechanism by which they influence cell growth. [ABSTRACT FROM AUTHOR]

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H2O2)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated β-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H2O2-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress. [ABSTRACT FROM AUTHOR]

Oral cancer is a leading cause of death, especially in developing countries. Head-and-neck squamous cell carcinoma is the sixth most common cancer worldwide. It accounts for 1.9% death annually due to delay in diagnosis and treatment strategies. Oral carcinogenesis is a multistep process. Recent advances in the understanding of the molecular control of these various pathways will facilitate more accurate diagnosis and assessment of prognosis and can pave the way for more novel approaches to treatment and prevention. This review highlights the major genes involved in oral carcinogenesis and emphasizes on the implementation of genomics, which can be the new paradigm for drug development and targeted therapeutics. [ABSTRACT FROM AUTHOR]

Background: Targeting Protein for Xenopus Kinesin Like Protein 2 (TPX2) is a microtubule associated protein that functions in mitotic spindle assembly. TPX2 also localizes to the nucleus where it functions in DNA damage repair during S-phase. We and others have previously shown that TPX2 RNA levels are strongly associated with chromosomal instability (CIN) in breast and other cancers, and TPX2 RNA levels have been demonstrated to correlate with aggressive behavior and poor clinical outcome across a range of solid malignancies, including breast cancer.Methods: We perform TPX2 IHC on a cohort of 253 primary breast cancers and adopt a clinically amenable scoring system to separate tumors into low, intermediate, or high TPX2 expression. We then correlate TPX2 expression against diverse pathologic parameters and important measures of clinical outcome, including disease-specific and overall survival. We link TPX2 expression to TP53 mutation and evaluate whether TPX2 is an independent predictor of chromosomal instability (CIN).Results: We find that TPX2 nuclear expression strongly correlates with high grade morphology, elevated clinical stage, negative ER and PR status, and both disease-specific and overall survival. We also show that increased TPX2 nuclear expression correlates with elevated ploidy, supernumerary centrosomes, and TP53 mutation. TPX2 nuclear expression correlates with CIN via univariate analyses but is not independently predictive when compared to ploidy, Ki67, TP53 mutational status, centrosome number, and patient age.Conclusions: Our findings demonstrate a strong correlation between TPX2 nuclear expression and aggressive tumor behavior, and show that TPX2 overexpression frequently occurs in the setting of TP53 mutation and elevated ploidy. However, TPX2 expression is not an independent predictor of CIN where it fails to outperform existing clinical and pathologic metrics. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the main genetic differences observed in high-grade gliomas (HGG) will present different MR imaging and MR spectroscopy correlates that could be used to better characterize lesions in the clinical setting. Methods: Seventy-nine patients with histologically confirmed HGG were recruited. Immunohistochemistry analyses for isocitrate dehydrogenase gene 1 (IDH1), alpha thalassemia mental retardation X-linked gene (ATRX), Ki-67, and p53 protein expression were performed. Tumour radiological features were examined on MR images. Metabolic profile and infiltrative pattern were assessed with MR spectroscopy. MR features were analysed to identify imaging-molecular associations. The Kaplan-Meier method and the Cox regression model were used to identify survival prognostic factors. Results: In total, 17.7% of the lesions were IDH1-mutated, 8.9% presented ATRX-mutated, 70.9% presented p53 unexpressed, and 22.8% had Ki-67 > 5%. IDH1 wild-type tumours had higher levels of mobile lipids (p = 0.001). The tumour-infiltrative pattern was higher in HGG with unexpressed p53 (p = 0.009). Mutated ATRX tumours presented higher levels of glutamate and glutamine (Glx) (p = 0.001). An association was observed between Glx tumour levels (p = 0.038) and Ki-67 expression (p = 0.008) with the infiltrative pattern. Survival analyses identified IDH1 status, age, and tumour choline levels as independent predictors of prognostic significance. Conclusions: Our results suggest that IDH1-wt tumours are more necrotic than IDH1-mut. And that the presence of an infiltrative pattern in HGG is associated with loss of p53 expression, Ki-67 index, and Glx levels. Finally, tumour choline levels could be used as a predictive factor in survival in addition to the IDH1 status to provide a more accurate prediction of survival in HGG patients. Key Points: • IDH1-wt tumours present higher levels of mobile lipids than IDH1-mut. • Mutated ATRX tumours exhibit higher levels of glutamate and glutamine. • Loss of p53 expression, Ki-67 expression, and glutamate and glutamine levels may contribute to the presence of an infiltrative pattern in HGG. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD), the prevalent dementia in the elderly, involves many related and interdependent pathologies that manifest simultaneously, leading to cognitive impairment and death. Amyloid-β (Aβ) accumulation in the brain triggers the onset of AD, accompanied by neuroinflammatory response and pathological changes. The CXCR4/CXCL12 (SDF1) axis is one of the major signal transduction cascades involved in the inflammation process and regulation of homing of hematopoietic stem cells (HSCs) within the bone marrow niche. Inhibition of the axis with AMD3100, a reversible antagonist of CXCR4 mobilizes endogenous HSCs from the bone marrow into the periphery, facilitating the recruitment of bone marrow-derived microglia-like cells into the brain, attenuates the neuroinflammation process that involves release of excitotoxic markers such as TNFα, intracellular Ca2 +, and glutamate and upregulates monocarboxylate transporter 1, the major L-lactate transporter in the brain.Objective: Herein, we investigate if administration of a combination of AMD3100 and L-lactate may have beneficial effects in the treatment of AD.Methods: We tested the feasibility of the combined treatment for short- and long-term efficacy for inducing endogenous stem cells' mobilization and attenuation of neuroinflammation in two distinct amyloid-β-induced AD mouse models.Results: The combined treatment did not demonstrate any adverse effects on the mice, and resulted in a significant improvement in cognitive/memory functions, attenuated neuroinflammation, and alleviated AD pathologies compared to each treatment alone.Conclusion: This study showed AMD3100's beneficial effect in ameliorating AD pathogenesis, suggesting an alternative to the multistep procedures of transplantation of stem cells in the treatment of AD. [ABSTRACT FROM AUTHOR]

Objective To investigate the value of combined determination of hepatitis C virus (HCV) genotype, the alpha - fetoprotein variant AFP - 13, and P53 antibody in HCV - related hepatocellular carcinoma (HCV - HCC). Methods A total of 84 patients with HCV - HCC who were diagnosed in our hospital from January 2016 to December 2019 were enrolled as HCV - HCC group, and 84 patients with benign liver diseases (hepatitis C and HCV liver cirrhosis) were enrolled as control group. The PCR - reverse dot blot hybridization technique was used to determine HCV genotype, ELISA was used to measure P53 antibody, and electrochemical luminescence was used to measure AFP - 13. The t - test and the Kruskal - Wallis H test were used for comparison between two groups; the chi - square test was used for comparison of categorical data between two groups. The logistic regression analysis and the receiver operating characteristic (ROC ) curve were used to compare the value of each index in the diagnosis of HCV - HCC. Results Compared with the control group, the HCV - HCC group had a significantly higher proportion of patients with H CV 1 b genotype or AFP - 13 and a significantly higher level of P53 antibody (x² = 5. 714, Z = - 9. 27, Z = － 9. 92, all P < 0. 05). The logistic regression analysis showed that HCV genotype, AFP - 13, and P53 antibody had significant effects on HCV - HCC (all P < 0. 05 ). The above indices were fitted to establish a model of Logit (Y) = - 3. 881 + 0. 031XAFP - L3(%) + O. 043XP53 + 1. 218XHCV genotype, in which Y was the positive probability value of combined determination. In the screening of HCV - HCC, Y had a significantly larger area under the ROC curve than HCV genotype (0. 945 vs 0. 758, Z = 6. 17, P < 0. 001), AFP -L3 (0. 945 vs 0. 863, Z = 3. 97, P <0. 001), and P53 antibody (0. 945 vs 0. 887, Z = 3. 07, P = 0. 002) . Y had higher AUC (0.945), sensitivity (90. 90%), specificity (94.00%), positive predictive value (93. 80%), negative predictive value (91.16%), and diagnostic accuracy (92. 44%) than each index alone. Conclusion HCV lb genotype, AFP-13, and P53 antibody level are associated with the risk of HCV - HCC, and the combined determination of the three indices has important clinical significance in the early diagnosis of HCV - HCC. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy among females worldwide. Recent studies have shown extra-ribosomal roles of the moonlight ribosomal proteins in the development of human cancers. Accurate quantification of the gene expression level is based on the selection of the reference genes whose expression is independent of cancer properties and patient's characteristics. The aim of this study was the evaluation of the expression level of a previously proposed ribosomal protein as moonlight, L13a (RPL13A), in breast cancer samples and their adjacent tissues. Its association with genes of known roles in developing cancers was also investigated. Traditionally used housekeeping genes were selected and their expression was analyzed in 80 surgically excised breast tissue specimens (40 tumors and 40 tumor-adjacent tissues) by applying three software tools including GeNorm, NormFinder, and BestKeeper to select the most stable reference genes. Then, mRNA expression levels of RPL13A and p53 were evaluated. Additionally, protein expression levels of RPL13A were measured. It was demonstrated that PUM1 and ACTB are the most reliable reference genes and RPL13A is the least stable gene. There was a positive correlation between RPL13A and p53 mRNA expression levels in all the tumor samples. Moreover, significant downregulation of RPL13A expression levels was revealed in HER2+ tumor samples compared to HER2- ones. There was also a marked decrease in p53 mRNA expression levels in HER2+ tumor subtypes. Our results suggest that there is a probable relationship between RPL13A decreased expression with p53 and HER2/neu expression in the breast cancer. [ABSTRACT FROM AUTHOR]

Background: Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study. Methods: Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-a (p53 inhibitor) or 10-[4'-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months. Results: DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-ß)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-a inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2). Conclusion: FGF21 prevents renal fibrosis via negative regulation of the TGF-ß/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway. [ABSTRACT FROM AUTHOR]

The p53 protein plays a number of roles in protecting organisms from different genotoxic stresses and this includes DNA damage induced by acetaldehyde, a metabolite of alcohol. Since the common tree shrew ingests high levels of alcohol as part of its normal diet, this suggests that its p53 protein may possess unique properties. Using a combination of biophysical and modeling studies, we demonstrate that the tetramerization domain of the tree shrew p53 protein is considerably more stable than the corresponding domain from humans despite sharing almost 90% sequence identity. Based on modeling and mutagenesis studies, we determine that a glutamine to methionine substitution at position 354 plays a key role in this difference. Given the link between stability of the p53 tetramerization domain and its transcriptional activity, the results suggest that this enhanced stability could lead to important consequences at p53-regulated genes in the tree shrew. • Stability of tree shrew p53 tetramerization domain is much higher than human p53. • Met354 in tree shrew sequence plays a key role in the stabilization. • These results may have important implications in using tree shrew as a model system. [ABSTRACT FROM AUTHOR]

Anti-angiogenic therapies are an important class of anti-cancer treatment drugs. However, their efficacy is limited to certain tumors and would benefit from identifying a biomarker predictive of therapeutic response. TP53 (tumor protein p53) is a tumor suppressor gene frequently mutated in cancer and implicated in cell-cycle regulation, apoptosis, and angiogenesis. Data from 7,525 unique tumor samples (representing 30 tumor cohorts) were retrieved from the TCGA database to analyze the relationship between TP53-mutation status and VEGFA (vascular endothelial growth factor A) expression. Univariate analyses were done using a Mann-Whitney univariate test or Fisher's exact test. Parameters with a p-value (p)≤0.1 in univariate analysis were selected for follow-up multivariate analyses, including TP53-mutation status, cancer cohorts, cancer subtypes, and VEGFA expression. Our analysis demonstrates statistically significant increases in VEGFA mRNA tissue expression in TP53-mutated adenocarcinomas (but not in squamous cancers) compared to TP53 wild-type tumors. This association holds true in multivariate analyses and remains independent of HIF-1α and MDM2 overexpression. Our findings provide additional evidence that TP53 mutations are linked to the VEGF pathway, potentially offering insight into the mechanism behind increased sensitivity to anti-angiogenic therapies observed in some TP53-mutant tumors. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the immunohistochemical expression of p53 in basal cell carcinoma of skin. Study Design: It was cross sectional study. Setting: Pathology department of Pakistan Institute of Medical Sciences Hospital, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan. Period: Six months from July 2015 to January 2016 after approval from the Hospital Ethical Committee. Material and Methods: In a descriptive background, 50 cases were involved in the study. Cases were selected by non-probability consecutive sampling technique. Patients of all age group (Males and Females), diagnosed as basal cell carcinoma of skin by Hematoxylin & Eosin were included in study. Other epithelial tumors of skin, appendageal tumors and metastatic tumors were excluded. Cases were evaluated for expression of tumor suppressor protein-p53 by immunohistochemical technique applied on formalin-fixed paraffinembedded blocks. Results: Out of 50 cases, majority of patients were found to be male. Ratio of male to female was 2.6:1. Age range of patient was found between 21-98 years. Mainstream of the patients were between 41-60 years. Nose was found to be frequently involved site 28 (56%) cases. p53 expression was seen in 42 (84%) cases while in 8 (16%) cases p53 expression was not seen. Conclusion: It was found that p53 expression rate is very high in basal cell carcinoma of skin. This high expression of p53 immunoreactivity was explained in terms of its pathogenetic role and mutation in basal cell carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Somatic TP53 mutation (TP53mut) is a characteristic finding in high-grade serous ovarian cancer (HGSOC). The aim of this study was to assess the clinical efficacy and utility of TP53mut circulating tumor DNA (ctDNA) monitoring as a biomarker for managing HGSOC. Methods: TP53muts were evaluated in patients who received primary treatment for suspected ovarian cancer at Asan Medical Center. In patients diagnosed with HGSOC and with TP53mut, ctDNA, cancer antigen 125 (CA 125), and computed tomography were followed up according to the treatment course. Results: Direct sequencing analysis of 103 tumor tissues from 61 HGSOC patients confirmed TP53muts in 41 patients (67.2%). All these patient-specific somatic mutations were detected in plasma cell-free DNA. The mean value of preoperative TP53 mutant allele count (TP53MAC) in stage III patients was 12.2 copies/µL and in stage IV patients was 45.3 copies/µL. TP53MAC was significantly reduced by treatment and there was no significant difference in the rate of decrease compared to CA 125 by the generalized linear mixed model. When patients were divided into a low TP53MAC group (<0.2 copies/µL) and a high TP53MAC group (=0.2 copies/µL) based on the TP53MAC value at 3 months after the end of chemotherapy, there was a significant difference in time to progression between the two groups (p=0.038). Conclusion: TP53mut ctDNA shows potential as a tumor-specific biomarker for treatment response monitoring in HGSOC. TP53mut ctDNA levels at 3 months post treatment has a significant prognostic utility than that of CA 125. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of cationic peroxidase from proso millet (PmPOD) on DNA damage and necroptosis in human colon cancer HCT116 and HT29 cells. Methods: Cell necroptosis and cell cycle was stained using Annexin V-FITC and cell cycle kits, respectively, and evaluated by flow cytometry. Lipid raft on the membrane was disrupted by cholesterol depletion and the location of PmPOD observed by confocal microscopy. Comet assays were used to detect DNA damage, and different inhibitors were also used. Knockdown of p53 or ectopic p53 expression in HCT116 cells were transfected p53 siRNA and pCMV3-TP53-myc plasmid, and p53 expression analyzed by western blotting. Results: Pre-treatment of HCT116 and HT29 cell lines with the specific necroptosis inhibitor Nec-1 prevented PmPOD-induced necroptosis, whereas the apoptosis inhibitor, z-VAD-fmk, had no effect. The entry of PmPOD is necessary for induction of DNA damage and necroptosis. Furthermore, PmPOD induced cell cycle arrest at S phase, as well as DNA DSBs in vivo, as reflected by numerous β-H2AX foci in CRC cells. However, the tumor suppressor protein, p53, alleviated PmPOD-induced DNA damage and necroptosis. Conclusions: These results demonstrate that PmPOD-induced DNA DSBs in CRC cells is the main cause of necroptosis, and that the tumor suppressor protein, p53, alleviates PmPOD-induced necroptosis by promoting p53-mediated repair pathways. [ABSTRACT FROM AUTHOR]

Objective: Extrinsic and intrinsic pathways of apoptosis are involved in generalized aggressive periodontitis (GAgP). The aim of this study was to evaluate 6‐month clinical outcomes relative to apoptosis of one‐stage full‐mouth disinfection (OSFMD) and systemic antibiotics (SA) in the treatment of GAgP. Methods: Twenty‐six patients with GAgP were included in this prospective follow‐up intervention study. Gingival crevicular fluid (GCF) was collected from patients at baseline and 3 and 6 months after periodontal therapy, which consisted of OSFMD and SA (amoxicillin and metronidazole, 500 mg each for 7 days). The levels of p53, caspase‐3, TNF‐α, TRAIL, IL‐1β, and IL‐10 in GCF were measured via ELISA. Results: Periodontal parameters were improved at 3 and 6 months compared to baseline (p < 0.05). p53 was decreased up to 6 months (p < 0.05). TRAIL, TNF‐α, and IL‐10 were similar at baseline and 3 and 6 months. Caspase‐3 and IL‐1β were decreased at 3 months (p < 0.05), but similar at 6 months compared to baseline (p > 0.05). Conclusion: Although OSFMD plus SA improves clinical periodontal parameters up to 6 months, this treatment protocol differentially regulates the apoptosis markers caspase‐3 at 3 months and p53 at 6 months without influencing TRAIL in GCF. [ABSTRACT FROM AUTHOR]

Background: Delanzomib, a novel proteasome inhibitor, has demonstrated promising efficacy and antitumor ability in human multiple myeloma cell lines and patient‐derived cells. However, the potential therapeutic effects of delanzomib on breast cancer remain unknown. In this study, we show that delanzomib has antitumor effects and synergizes with doxorubicin (Dox) in human breast cancer cell lines. Methods: Cell proliferation assay and flow cytometry were used to evaluate cell viability and apoptosis in eight human breast cancer cell lines after treatment with delanzomib or Dox. Essential molecules of the p53, MAPK, and apoptosis signaling pathways were analyzed by Western blotting. Results: Delanzomib induced cell death and demonstrated synergism with Dox in all tested breast cancer cell lines. In addition, delanzomib enhanced the Dox‐induced phosphorylation of p38/JNK and the expression of transcriptional target proteins of p53, such as p21, p27, NOXA, and PUMA. Conclusion: The combined regimen of the proteasome inhibitor delanzomib with Dox chemotherapy may become an effective strategy for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of P53 and its correlation with clinicopathological characteristics in invasive breast cancer. Methods A total of 709 cases of invasive breast cancer were collected in the Nantong Cancer Hospital from January 2015 to December 2017. The expressions of P53 in 709 cases were detected with immunohistochemistry. The expression of P53 and its correlation with molecular classifications, histologic grades and expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and Ki-67 were investigated and analyzed. Results The high positive rate of P53 was 26.8% (190/709), low positive rate of P53 was 73.2% (519/709). The high positive rate of P53 in luminal subtype A, luminal subtype B with negative HER-2, luminal subtype B with positive HER-2, HER-2 over-expressing subtype and triple negative subtype were 6.1% (12/197), 18.0% (34/189), 39.1% (25/64), 50.0% (58/116) and 42.7% (61/143), respectively. There were significant differences in expressions of P53 between five luminal subtypes (P＜0.05). The expression level of P53 was higher in breast cancer with medullary histological features than that in other histologic subtypes (P＜0.05). The expression of P53 increased with the rise of histologic grades (P＜0.05). The expression level of P53 was higher in breast cancer with ER negative, PR negative, HER-2 positive and high Ki-67 expression groups (all P＜0.05). Conclusion P53 plays a significant role in the development and progression of invasive breast cancer. The expression of P53 can be used to guide the individualized therapy and as a reference index to clinical outcome prediction in invasive breast cancer. [ABSTRACT FROM AUTHOR]

Apoptosis stimulating protein of p53 2 (ASPP2) is a member of the apoptosis stimulating proteins of p53 and can specifically bind to the core region of p53 protein and enhance the ability of p53 to promote transcription of apoptotic genes. At present, it is believed that ASPP2 plays an important role in regulating cell apoptosis, autophagy, proliferation and affecting the progression of inflammation and tumors. This article summarizes the main biological functions of ASPP2 and the research advances in the role of ASPP2 in hepatocellular carcinoma, hepatitis C, and nonalcoholic fatty liver disease. Studies have shown that ASPP2 can regulate cell apoptosis and may be a potential therapeutic target for a variety of diseases. [ABSTRACT FROM AUTHOR]

The etiology of recurrent spontaneous abortion (RSA) is very complex, and about 50% of cases are undefined. The repeated loss of the embryo caused by the damaged decidualization is a research hotspot. p53 mediates the deterioration of decidualization by participating in multiple signaling pathways, leading to recurrent abortion. The excessive activation of p53/p21 signaling pathway can interfere the expressions of those regulatory factors related to cell cycle which make the blockage of cell cycle, induce the decidualization, promote the apoptosis, and affect the embryonic implantation. In the E2/p53 -leukemia inhibitory factor (LIF) -signal transduction and transcriptional activator factor 3 (STAT3) signaling pathway, p53 promotes the secretion of LIF by the endometrial gland during the implantation period under the synergistic effect of estrogen, and activates JAK/ STAT signaling pathway, creating favorable conditions for embryonic implantation. Moreover, studies have shown that the functional abnormality of lncRNA involved in regulating p53 signaling pathway and the polymorphism of p53 pathway genes could affect the activity of p53, and decidualization and pregnancy outcome. The recent studies on p53 protein family and its pathways involved in decidualization were reviewed. [ABSTRACT FROM AUTHOR]

Chronic diseases including coronary artery disease (CAD) impose a high burden in terms of mortality and disability particularly in developing countries. Both genetic and environmental risk factors confer susceptibility to CAD. Meanwhile, a functional polymorphism in the tumor protein p53 (TP53) gene (codon 72, exon 4) has been reported to be associated with a wide range of cancers and inflammatory disorders. There are controversies regarding CAD and involvement of the TP53 codon 72 single nucleotide polymorphism; therefore, the present case-control study was conducted to evaluate the potential association between this TP53 polymorphism and CAD in an Iranian population. A total of 153 subjects (including 70 patients diagnosed with CAD and 83 subjects with normal coronary parameters, determined by angiography) were genotyped for the TP53 (rs1042522) polymorphism by the polymerase chain reaction-restriction fragment length polymorphism technique. Clinical and laboratory findings were also evaluated. The χ2 test and unpaired Student's t-test were applied to compare genotype and allele distributions and clinical characteristics between the two groups. Significant associations of the Pro72 allele [odds ratio (OR)=1.66, P=0.027] and Pro/Pro genotype (OR=2.91, P=0.022) with CAD were identified. No associations between patients' clinical findings and genotypes were apparent. Therefore, according to present findings, the TP53 Pro72 allele may be involved in the development of CAD along with conventional risk factors in patients from Northern Iran. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. DNA damage repair in cancer cells is a promising approach for the treatment of cancers. We aimed to explore the potential interaction between p53-binding protein 1 (53BP1) and minichromosome maintenance (MCMs) proteins during DNA damage in human hepatoma HepG2 cells. Methods: The recombinant vectors of 53BP1 and MCMs with tags were constructed and transfected into HepG2 cells. Immunoprecipitation (IP) and mass spectrometry (MS) were performed to identify the possible interactions between 53BP1 and MCMs, and glutathione S-transferase (GST) pull-down assay was carried out to detect the direct interaction. Moreover, the expressions of MCM2 and MCM6 were suppressed by specific short hairpin RNAs (shRNAs), and then the chromatin fraction and foci formation of 53BP1 were examined under the condition of DNA damage. Results: The results showed that MCM2/3/5/6 was immunoprecipitated against the hemaglutinin (HA)-tagged 53BP1 in HepG2 cell nuclei. GST results revealed that there was a direct interaction between 53BP1 and MCMs complex. Moreover, the non-chromatin level of 53BP1 was significantly increased by down-regulation of MCM2 or MCM6, but was statistically decreased the chromatin level. Furthermore, we observed that knockdown of MCM2 or MCM6 could statistically inhibit the foci formation of 53BP1 in HepG2 cell nuclei upon bleomycin-induced DNA damage (P < 0.01). Conclusion: Our results suggest that there is a direct interaction between 53BP1 and MCMs, which is essential for 53BP1 chromatin fraction and foci formation in hepatoma HepG2 cells. [ABSTRACT FROM AUTHOR]

A functional electrospun nanofibers-based electrochemiluminescence (ECL) immunosensor for detection of the tumor suppressor protein p53 (TSP 53 ) at trace level using core-shell nanocomposite as signal enhancers is fabricated. The gold nanoparticles (AuNPs) were decorated on the surface of the electrospun carbon-nanotubes (MWCNTs) doped chitosan (CTS) nanofibers (MWCNTs-CTS) by in-situ electrodeposition. The functional electrospun nanofibers (MWCNTs-CTS-AuNPs) was utilized as supporting scaffolds for TSP 53 capture antibody (C Ab ) immobilization firstly. They can dramatically increase the amount and stability of C Ab attachment, and efficiently enhance the sensitivity of detection. After a sandwich immunoreaction, TSP 53 and Ru(bpy) 3 2+ /silver nanoparticles doped silica core-shell nanocomposite (RuAg/SiO 2 NPs)-labeled detection antibody (RuAg/SiO 2 NPs@D Ab ) captured onto the electrode surface. It was observed that the increase of response ECL signal was proportional to the TSP 53 concentration in the range of 1 pg mL −1 to 1 ng mL −1 . The detection limit was 0.5 pg mL −1 , which is comparable or better than that in reported TSP 53 assays. The immunosensor was successfully applied to determination of TSP 53 in normal human cubital vein blood samples with good recovery, and the results are basically consistent with the TSP 53 Kit (ELISA). Excellent sensitivity and selectivity make the developed ECL immunosensor a potential and simple tool for the detection of tumor biomarkers. [ABSTRACT FROM AUTHOR]

Background/Aims: Chronic liquid and/or food stasis caused by retention esophagitis (RE) in achalasia is a notable endoscopic finding because of the presence of a thickened or whitish esophageal mucosa and histologically altered squamous hyperplasia. We aimed to identify the clinical features of RE associated with achalasia and to clarify the clinical definition of RE in achalasia as a precancerous lesion identified by analyzing biomarker expressions. Methods: From 2006 to 2015, we retrospectively reviewed 37 patients with achalasia without previous treatment. Among them, 21 patients had diagnostic findings of RE (RE+) and 16 patients had no diagnostic findings of RE (RE-). Immunohistochemical staining of p53, p16, and Ki-67 was performed on the endoscopic biopsy tissues from the patients with achalasia and 10 control patients with non-obstructive dysphagia. Results: The symptom duration and transit delay were significantly longer in the RE+ group than in the RE-group. We found particularly high p53 positivity rates in the RE+ group (p<0.001). The rate of p16 expression was also significantly higher in the RE+ group than in the other two groups (p=0.003). Conclusions: A high p53 expression rate was more frequently found in the RE+ group than in the other two groups. RE could be a meaningful clinical feature of achalasia for predicting esophageal carcinogenesis. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia is a chronic progressive disorder affecting the nervous and immune systems, caused by a genetic defect in the ATM protein. Clasmatodendrosis, a distinct form of astroglial death, has rarely been reported in ataxia-telangiectasia. Neuropathology of our patient disclosed diffuse edema of the cerebral and cerebellar white matter with prominent clasmatodendrosis, implicating ATM in the regulation of astroglial cell death. [ABSTRACT FROM AUTHOR]

This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 pa- tients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC. [ABSTRACT FROM AUTHOR]

Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa , have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes’ type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes’ type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes’ type C metastatic stage. [ABSTRACT FROM AUTHOR]

Purpose: TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC). Materials and Methods: We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients. Results: Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57, respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patients with a TP53missense mutation (5-year distant recurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316). Conclusion: Association between TP53mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients. [ABSTRACT FROM AUTHOR]

Background/Aim. Pterygium is considered to be a degenerative disease of the conjunctiva, however, the presence of tumor markers in pterygium reinforces the hypothesis that this lesion is similar to tumor. Inactivation of p53 function removes an obstacle to increased proliferation. Factors affecting the prevalence of p53 expression in pterygium deserve investigation. The aim of the study was to investigate the expression of p53 and Ki-67 proteins in pterygium and normal conjunctiva, the effects of gender and age on p53 expression, and the relationship between the expression of p53 and Ki-67 proteins. Methods. A total of 34 samples of pterygium and 34 samples of the normal conjunctiva were analyzed. The samples were studied by immunohistochemistry using antibodies against p53 and Ki-67. Results. Totally 15 (44%) samples of pterygia were p53 positive. Correlations between the expression of p53 protein and sex, and age were not established. The number of Ki-67 positive cells in pterygium (9.74%) was significantly higher than the number of Ki-67 positive cells in the normal conjunctiva (1.74%), (p = 0.001). Between the expression of p53 protein and Ki-67 protein in pterygium there was a significant positive correlation (p = 0.000). Conclusion. The prevalence of p53 positive samples of pterygium was 44%. The influence of sex and age on p53 protein expression in pterygium was not found. The increased proliferative acivity was present in the epithelium of pterygium. The expression of Ki-67 protein is associated with the expression of p53 protein in pterygium. The findings of our study support the thesis of pterygium as tissue growth disorder. [ABSTRACT FROM AUTHOR]

An enzyme electrocatalytic immunosensor based on functional composite nanofibers for sensitive detection of tumor suppressor protein p53 (AG p53 ) is developed. The carboxylated multi-walled carbon nanotube (MWCNT) doped nylon 6 (PA6) composite nanofibers (MWCNT-PA6) were prepared using electrospinning, which served as the nanosized backbone for thionine (TH) electropolymerization. The functional composite nanofibers (MWCNT-PA6-PTH) served as supporting scaffolds not only promotes electron transfer, but also increases the surface area to introduce a large amount of AG p53 capture antibody (Ab 1 ), thus increasing the detection sensitivity. After a sandwich immunoreaction, AG p53 and horseradish peroxidase (HRP)-labeled detection antibody (HRP@Ab 2 ) captured onto the electrode surface produced an amplified electrocatalytic response by the reduction of enzymatically oxidized polythionine (PTH) in the presence of hydrogen peroxide (H 2 O 2 ). The increase of response current was proportional to the AG p53 concentration in the range of 2 pg mL − 1 to 2 ng mL − 1 and the detection limit was down to 1 pg mL − 1 . This study provides new insight into the design of advanced electrospun nanofiber-based immunosensor for detection and analysis of a variety of proteins. It holds promise for the diagnosis of cancer development and monitoring of patient therapy. [ABSTRACT FROM AUTHOR]

As a tumor suppressor, p53 is activated by numerous cellular and environmental signals, and plays a critical role in the cell cycle regulation, cell apoptosis and senenscence. The murine double minute (MDM)2 and double minute mu⁃ rine 4 (MDMX) are two important regulators. MDMX is a p53 binding protein with strong sequence homology to MDM2, but lacks ubiquitin ligase activity, and which is unable to target p53 for proteasomal degradation. MDMX regulates p53 activity through its binding with p53 and its postranscriptional modification. MDMX in the closed and open structure binds to p53 to regulate its activity. As the main partner of MDMX, casein kinase 1 alpha (CK1α) disrupts the intramolecular binding in MD⁃ MX in the cooperation to regulate p53 activity. The process of MDMX and CK1α in the regulation of p53 is multi-step and complicated. In this paper the mechanism of MDMX and CK1α in the regulation of p53 protein was reviewed. [ABSTRACT FROM AUTHOR]

The tumor protein p53 gene (TP53) mutations are associated with poor prognosis of patients with acute myeloid leukemia (AML). This study aimed to establish TP53 mutation-based prognostic risk signatures. The transcriptomes and clinical characteristics of AML patients were acquired from The Cancer Genome Atlas database, including 11 TP53 -mutant samples and 114 TP53 -wildtype samples. Differentially expressed mRNAs and long non-coding RNAs (lncRNA) in TP53 -mutant samples were identified. Weighted gene correlation network analysis was performed to generate survival-associated co-expression modules. LASSO regression analysis was conducted to build mRNA- and lncRNA-based prognostic risk signatures. Kaplan-Meier curve analysis and multivariate regression analysis were carried out to assess the prognostic values of the risk signatures. Receiver operating characteristic (ROC) analysis was performed to evaluate the accuracy of the signatures. Based on the co-expression modules, a 5-mRNA risk signature and a 13-lncRNA risk signature were constructed to predict the overall survival for AML patients. Kaplan-Meier curves revealed that the high-risk patients had significantly shorter overall survival than the low-risk patients. ROC analysis yielded 1-, 3-, and 5-year AUCs of 0.681, 0.783, and 0.827 for mRNA signature and 0.85, 0.835, and 0.908 for lncRNA signature. Multivariate regression analysis revealed that both mRNA (HR = 1.45, P < 0.001) and lncRNA (HR = 1.19, P < 0.001) risk scores were independent prognostic factors for AML patients. We provided a potential patients stratification tool for AML prognosis prediction and management, which established by effective TP53 mutation-related gene signatures. [ABSTRACT FROM AUTHOR]

BACKGROUND: In addition to ultraviolet radiation exposure, various molecular markers may differ between oral mucosal and cutaneous head and neck melanomas and lead to variations in their biologic behavior and prognosis. The aim of this study was to compare four such markers, namely microphthalmia transcription factor (MITF), P75, P53, and Ki-67 in malignant melanomas originating from the oral cavity and head and neck skin. METHODS: A total of 19 oral mucosal and 23 head and neck cutaneous melanomas were subjected to immunohistochemical analysis using antibodies against MITF, P75, P53, and Ki-67. Statistical comparison of data was performed by t-test and chi-square analysis (P < 0.05). RESULTS: Significant differences in MITF (P = 0.016) and Ki-67 (P = 0.002) were observed between oral mucosal and cutaneous melanomas. P75 (P = 0.80) and P53 (P = 0.76) did not differ significantly, between these locations. CONCLUSIONS: According to the results obtained in this study, the biological properties of cutaneous and mucosal melanoma differ, especially regarding MITF and Ki-67. [ABSTRACT FROM AUTHOR]

Background FUSE binding protein1 (FBP1) is a transactivator of transcription of human c-myc proto-oncogene and expressed mainly in undifferentiated cells. It is also present in differentiated normal cells albeit with very low background. FBP1 is abundantly expressed in the majority of hepatocellular carcinoma tumors and has been implicated in tumor development. Although it down-regulates the expression of proapoptotic p21 protein, it is not known whether FBP1 also interacts and antagonizes the function of tumor suppressor protein p53. Methods Western blotting was carried out to detect the expression level of FBP1, p21 and p53, and also p53 regulatory factors, BCCIP and TCTP; real-time quantitative PCR was done to determine the fold change in mRNA levels of target proteins; immunoprecipitation was carried out to determine the interaction of FBP1 with p53, BCCIP and TCTP. Cells stably knockdown for either FBP1; p53 or BCCIP were examined for p53 reporter activity under normal and radiation-induced stress. Results FBP1 physically interacted with p53, impairing its transcription activity and reducing p53- mediated sensitivity to cellular stress. Knockdown of FBP1 expression activated p53- mediated response to cellular stress while transient expression of FBP1 in FBP-knockdown cells restored the inhibition of p53 activity. FBP1 not only interacted with both BCCIP and TCTP, which, respectively, function as positive and negative regulators of p53, but also regulated their expression under cellular stress. In FBP knockdown cells, TCTP expression was down-regulated under radiation-induced stress whereas expression of BCCIP and p21 were significantly up-regulated suggesting FBP1 as a potential regulator of these proteins. We hypothesize that the FBP1-mediated suppression of p53 activity may occur via preventing the interaction of p53 with BCCIP as well as by FBP1-mediated regulation of p53 regulatory proteins, TCTP and BCCIP. Since FBP1 suppresses p53 activity and is overexpressed in most HCC tumors, it may have a possible role in tumorigenesis. Conclusion FBP1 physically interacts with p53, functions as a regulator of p53-regulatory proteins (TCTP and BCCIP), and suppresses p53 transactivation activity under radiation-induced cellular stress. Since it is abundantly expressed in most HCC tumors, it may have implication in tumorigenesis and thus may be a possible target for drug development. [ABSTRACT FROM AUTHOR]

Objective To investigate the anti-tumor effect and mechanism of curcumin in pancreatic cancer (PC). Methods Smad4 and Jab1 expressions were detected by immunohistochemistry in tumor tissues and pericarcinomatous tissue from 35 PC cases, and the correlation of Smad4 and Jab1 were analyzed based on the percentage of positive staining intissues from 21 random selected PC cases. The effect of curcumin on expressions of tumor suppressors p53, Smad4 and cell cycle inhibitor p27 were examined by Western Blotting after human pancreatic cancer cell line PANC-1 were divided into PANC-1 control group (no treatments were given) and PANC-1 curcumin group (treated with cell culture medium containing 10 μmol/L curcumin). The effect of curcumin on expressions of combination of β-TrCP1 and Smad4 was examined by Co-Immunoprecipitation after human embryonic kidney cell line 293T were divided into 293T control group (no treatments were given), 293T curcumin group (treated with cell culture medium containing 10 μmol/L curcumin) and 293T Jab1 group (transfected by HA-Jab1 plasmid). Results Compared with expressions in pericarcinomatous tissues, Smad4 was down regulated while the expression of Jab1 was upregulated in PC tissues (P < 0.01), and the expression of Smad4 was negatively correlated with the expression of Jab1 (n=21, r=-0.71, P=0.007). After treated with curcumin, the protein expression of p53, Smad4 and p27 was increased in PANC1 cell, and the protein expression of the combination of β-TrCP1 and Smad4 was decreased in 293T cell (P < 0.05). After transfected by HA-Jab1 plasmid, the protein expression of the combination of β-TrCP1 and Smad4 was increased in 293T cell (P < 0.05). Conclusion Curcumin may have suppression effect of PC through increasing the protein expression of p53, Smad4 and p27, and the mechanism of Smad4 upregulation may be related with the inhibition of Smad4 ubiquitination process, while Jab1 may be also involved in Smad4 degradation through ubiquitination. [ABSTRACT FROM AUTHOR]