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Copyright of Tianjin Medical Journal is the property of Tianjin Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background & Objective: The regulator of chromosome condensation 2 (RCC2) and RAS-related C3 botulinum toxin substrate 1 (Rac1) have been implicated in the promotion of breast cancer cell proliferation and migration. The signaling pathway involving p53/RCC2/Rac1 has been proposed to contribute to the regulation of colon cancer metastasis. However, until now, this pathway has not been thoroughly investigated in breast cancer. This study seeks to explore the influence of immunohistochemical expression and the correlation among RCC2, Rac1, and p53 in breast infiltrating ductal carcinoma (IDC). Methods: Immunostaining was performed on 120 breast IDC specimens using RCC2, Rac1, and p53 antibodies. Statistical analyses were conducted to examine the correlations between these antibodies. Results: A Positive expression of RCC2, Rac1, and p53 was observed in 116 (96.7%), 120 (100%), and 33 (27.5%) of the breast cancer cases, respectively. RCC2, Rac1, and p53 demonstrated association with poor prognostic parameters such as frequent mitoses, high Ki-67 status, positive lymphovascular invasion (LVI), and advanced tumor stage. A highly significant direct correlation was found between each immunohistochemical marker and the other two markers. Shorter overall survival was linked to multifocal tumors (P=0.017), advanced tumor stage (T3) (P=0.010), Luminal B subtype (P=0.015), progressive disease (P=0.003), positive Her2neu status (P=0.008), and metastasis to distant organs (P<0.001). However, RCC2, Rac1, and p53 did not exhibit a significant association with overall survival. Conclusion: The high expression levels of RCC2, Rac1, and p53 in breast IDC suggest their potential role in tumor behavior. The association of RCC2 and Rac1 with poor prognostic parameters may serve as predictive indicators for aggressive tumors, thus implying that targeted therapy could be beneficial in the treatment of breast cancer. [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: 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]

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]

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]

Introduction: This study investigates the impact of two high-intensity interval training (HIIT) programs on PGC-1a, p53, and citrate synthase (CS) proteins within cardiomyocytes of male type 2 diabetic rats, aiming to discern potential molecular mechanisms influencing cardiac health. Material & Methods: Twenty-four male Wistar rats were randomly assigned to control (NC), diabetic control (DC), diabetic with type 1 HIIT (HIIT-1), and diabetic with type 2 HIIT (HIIT-2) groups. Streptozotocin (STZ) induced type 2 diabetes, excluding the NC group. A four-week HIIT intervention, six sessions per week, preceded the analysis of heart tissue for PGC-1a, p53, and CS protein levels. Statistical analysis employed GraphPad Prism software version 8 and one-way ANOVA (P < 0.05). Results: Both HIIT-1 (p=0.004) and HIIT-2 (p=0.007) groups exhibited significantly elevated cardiac PGC-1a levels compared to DC. CS levels increased notably in HIIT-1 (p=0.001) and HIIT-2 (p<0.001), with HIIT-2 surpassing HIIT-1 significantly (p=0.010). Concurrently, p53 levels significantly decreased in both HIIT-1 (p=0.005) and HIIT-2 (p=0.001) groups compared to DC. Conclusion: Exercise training (HIIT) positively influences cardiac metabolism, evident in PGC-1a and CS upregulation and p53 downregulation. While these findings provide valuable insights, further exploration is crucial for a comprehensive understanding of the underlying molecular mechanisms. This study advances our understanding of optimizing exercise interventions for improved cardiac health in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a prevalent gastrointestinal neoplasm that ranks fourth in terms of cancer-related deaths worldwide. In the process of CRC progression, multiple ubiquitin-conjugating enzymes (E2s) are involved; UBE2Q1 is one of those newly identified E2s that is markedly expressed in human colorectal tumors. Since p53 is a well-known tumor suppressor and defined as a key factor to be targeted by the ubiquitin–proteasome system, we hypothesized that UBE2Q1 might contribute to CRC progression through the modulation of p53. Using the lipofection method, the cultured SW480 and LS180 cells were transfected with the UBE2Q1 ORF-containing pCMV6-AN-GFP vector. Then, quantitative RT-PCR was used to assay the mRNA expression levels of p53's target genes, i.e., Mdm2, Bcl2, and Cyclin E. Moreover, Western blot analysis was performed to confirm the cellular overexpression of UBE2Q1 and assess the protein levels of p53, pre- and post-transfection. The expression of p53's target genes were cell line-dependent except for Mdm2 that was consistent with the findings of p53. The results of Western blotting demonstrated that the protein levels of p53 were greatly lower in UBE2Q1-transfected SW480 cells compared to the control SW480 cells. However, the reduced levels of p53 protein were not remarkable in the transfected LS180 cells compared to the control cells. The suppression of p53 is believed to be the result of UBE2Q1-dependent ubiquitination and its subsequent proteasomal degradation. Furthermore, the ubiquitination of p53 can act as a signal for degradation-independent functions, such as nuclear export and suppressing the p53's transcriptional activities. In this context, the decreased Mdm2 levels can moderate the proteasome-independent mono-ubiquitination of p53. The ubiquitinated p53 modulates the transcriptional levels of target genes. Therefore, the up-modulation of UBE2Q1 may influence the transcriptional activities depending on p53, and thereby contributes to CRC progression through regulating the p53. [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]

Copyright of Tianjin Medical Journal is the property of Tianjin Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Clinical Neurosurgery / Linchuang Shenjingwaike Zazhi is the property of Editorial Board of Journal of Clinical Neurosurgery and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cocoa, rich in polyphenols, has been reported to provide many health benefits due to its antioxidant properties. In this study, we investigated the effect of Cocoa polyphenols extract (CPE) against oxidative stress-induced cellular senescence using a hydrogen peroxide (H2O2)-induced cellular senescence model in three auditory cells lines derived from the auditory organ of a transgenic mouse: House Ear Institute-Organ of Corti 1 (HEI-OC1), Organ of Corti-3 (OC-k3), and Stria Vascularis (SV-k1) cells. Our results showed that CPE attenuated senescent phenotypes, including senescence-associated β-galactosidase expression, cell proliferation, alterations of morphology, oxidative DNA damage, mitochondrial dysfunction by inhibiting mitochondrial reactive oxygen species (mtROS) generation, and related molecules expressions such as forkhead box O3 (FOXO3) and p53. In addition, we determined that CPE induces expression of sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3), and it has a protective role against cellular senescence by upregulation of SIRT1 and SIRT3. These data indicate that CPE protects against senescence through SIRT1, SIRT3, FOXO3, and p53 in auditory cells. In conclusion, these results suggest that Cocoa has therapeutic potential against age-related hearing loss (ARHL). [ABSTRACT FROM AUTHOR]

Long-term survival in patients with acute myeloid leukemia (AML) remains low, and current treatment modalities are inadequate. Milademetan (DS-3032, RAIN-32), a small-molecule specific murine double minute 2 inhibitor, has shown a p53 status-dependent antitumor effect in vitro studies. This is the first phase I study report of milademetan monotherapy in relapsed/refractory (R/R) AML patients evaluating the safety, tolerability, pharmacokinetics, and preliminary tumor response for further clinical development. Fourteen patients received 90 (starting dose, n = 4), 120 (n = 6), or 160 mg (n = 4) of oral milademetan once daily in a 14/28 treatment cycle. The median total treatment duration was 1.5 cycles. Dose-limiting toxicity did not occur, and the maximum tolerated dose was not reached. Thus, the recommended dose was defined as 160 mg. The most common adverse events (AEs) were decreased appetite (64.3%), febrile neutropenia (50%), nausea (42.9%), and anemia (35.7%). No deaths or AEs leading to treatment discontinuation occurred. Five serious treatment-emergent AEs occurred in 4 patients. Plasma concentration increased linearly with milademetan dose. However, trends in the safety and efficacy of oral milademetan in patients with R/R AML warrant further clinical investigation. This study can inform future milademetan studies in hematologic malignancies. [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]

Purpose: This project aimed to assess the significance of vascular endothelial growth factor (VEGF) and p53 for predicting progression-free survival (PFS) in patients with spinal giant cell tumor of bone (GCTB) and to construct models for predicting these two biomarkers based on clinical and computer tomography (CT) radiomics to identify high-risk patients for improving treatment. Material and Methods: A retrospective study was performed from April 2009 to January 2019. A total of 80 patients with spinal GCTB who underwent surgery in our institution were identified. VEGF and p53 expression and clinical and general imaging information were collected. Multivariate Cox regression models were used to verify the prognostic factors. The radiomics features were extracted from the regions of interest (ROIs) in preoperative CT, and then important features were selected by the SVM to build classification models, evaluated by 10-fold crossvalidation. The clinical variables were processed using the same method to build a conventional model for comparison. Results: The immunohistochemistry of 80 patients was obtained: 49 with high-VEGF and 31 with low-VEGF, 68 with wild-type p53, and 12 with mutant p53. p53 and VEGF were independent prognostic factors affecting PFS found in multivariate Cox regression analysis. For VEGF, the Spinal Instability Neoplastic Score (SINS) was greater in the high than low groups, p < 0.001. For p53, SINS (p = 0.030) and Enneking stage (p = 0.017) were higher in mutant than wild-type groups. The VEGF radiomics model built using 3 features achieved an area under the curve (AUC) of 0.88, and the p53 radiomics model built using 4 features had an AUC of 0.79. The conventional model built using SINS, and the Enneking stage had a slightly lower AUC of 0.81 for VEGF and 0.72 for p53. Conclusion: p53 and VEGF are associated with prognosis in patients with spinal GCTB, and the radiomics analysis based on preoperative CT provides a feasible method for the evaluation of these two biomarkers, which may aid in choosing better management strategies. [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]

Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The ubiquitin-proteasome system is regulated by deubiquitinating enzymes (DUBs), which include the complex Ubiquitin-specific protease 1 (USP1) and WD40 repeat-containing protein 48 (WDR48). In normal conditions, these proteins contribute to genome integrity by regulating the DNA repair pathways. However, studies have associated abnormalities in this complex with the pathogenesis of cancer. Simultaneously, Tumor Suppressor Protein p53 is also regulated by ubiquitin-dependent degradation and its overexpression suggests that several DUBs are interacting and deubiquitinating this protein. Objective: To evaluate the immunoexpression of p53, USP1, and WDR48 in Oral Squamous Cell Carcinoma (OSCC). Material and methods: Thirty cases of OSCC and 40 non-neoplastic oral epithelium (NNOE, control group) were selected for immunohistochemical investigation. The histopathological classification was performed using H&E-stained sections. Values were statistically analyzed using the non-parametric test Kruskal Wallis. Results: Higher positivity of the markers was found in OSCC (p53:65%; USP1:96.4%; WDR48: 68.9%) than in NNOE (p53:35.1%; USP1:85%; WDR48: 65.2%). Poorly-differentiated cases of OSCC exhibited higher nuclear immunostaining of all proteins when compared with well-differentiated samples. Conclusion: This is a pioneer study and suggests that p53 and deubiquitinating enzymes (USP1 and WDR48) can affect the biological behavior of OSCC as they are related to the tumor development and histological malignancy grading. [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]

Copyright of Genetika (0534-0012) is the property of Serbian Genetics Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Purpose: The aim of this study was to determine whether the outcome to neoadjuvant chemotherapy (NAC) can be predicted by analyzing p53 expression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients. Methods: We retrospectively reviewed 594 patients diagnosed with stage I–III HR-positive, HER2-negative breast cancer, and treated with NAC at the Asan Medical Center between 2008 and 2014. Expression of p53 was assessed, and overall survival (OS) and breast cancer-specific survival (BCSS) were investigated and compared between groups. Results: At a median follow-up period of 69.8 months, OS and BCSS were higher in the p53-negative (p53(−)) group than in the p53-positive (p53(+)) group. Five-year OS was 95.4% in the p53(−) and 92.1% in the p53(+) group (p = 0.005). BCSS was 96.2% in the p53(−) group and 93% in the p53(+) group (p = 0.008). Conclusion: High expression of immunohistochemically detected p53 was strongly and significantly associated with decreased OS and BCSS than low p53 expression, suggesting that p53 may be a powerful prognostic factor in HR-positive, HER2-negative breast cancer patients receiving NAC. [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]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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: 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]

Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Tianjin Medical Journal is the property of Tianjin Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Copyright of Journal of International Reproductive Health/Family Planning is the property of Editorial Board of the Journal of International Reproductive Health/Family Planning and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

Replication stress is a major source of DNA damage and an important driver of cancer development. Replication intermediates that occur upon mild forms of replication stress frequently escape cell cycle checkpoints and can be transmitted through mitosis into the next cell cycle. The consequences of such inherited DNA lesions for cell fate and survival are poorly understood. By using time-lapse microscopy and quantitative image-based cytometry to simultaneously monitor inherited DNA lesions marked by the genome caretaker protein 53BP1 and cell cycle progression, we show that inheritance of 53BP1-marked lesions from the previous S-phase is associated with a prolonged G1 duration in the next cell cycle. These results suggest that cell-to-cell variation in S-phase commitment is determined, at least partially, by the amount of replication-born inherited DNA damage in individual cells. We further show that loss of the tumor suppressor protein p53 overrides replication stress-induced G1 prolongation and allows Sphase entry with excessive amounts of inherited DNA lesions. Thus, replication stress and p53 loss may synergize during cancer development by promoting cell cycle re-entry with unrepaired mutagenic DNA lesions originating from the previous cell cycle. [ABSTRACT FROM AUTHOR]

The protein p53 is considered to be one of the most important tumor suppressor factors. Despite this importance, a potential association between TP53 messenger (m)RNA levels and tumor aggressiveness has not been well defined in animal cancer. We assessed and correlated TP53 gene expression in 40 canine mammary carcinomas with histologic grade, tumor size, and aggressiveness. The tumors were subjected to histologic analysis and the TP53 mRNA levels determined by RT-rtPCR. Statistical analysis revealed no correlation between levels of TP53 mRNA and tumor aggressiveness (r = 0.00) or tumor growth (r = 0.06). Histologic grades (r = 0.17) and mitosis count (r = 0.12) showed a weak correlation with TP53 mRNA expression levels. These findings are consistent with molecular studies that revealed heterogeneous expression of TP53 in canine and human mammary tumors. Hence, TP53 gene expression alone cannot be considered a marker for tumor aggressiveness in canine mammary carcinomas. [ABSTRACT FROM AUTHOR]

Aim. This systematic review is aimed at evaluating the literature on the efficacy of naturally available extracts that inhibit cancer. Methods. A literature search was performed to strengthening the reporting of observational studies in epidemiology analysis. Approximately 3000 research articles were initially selected. Of these articles, 200 were included, and 2800 were excluded. On further scrutiny, 150 of the 200 studies were reviews, seminars, and presentations, and 50 were original study articles. Among these articles, 20 studies were selected for the systematic review. Results. The predominant molecular pathways followed by natural extracts were nuclear factor kappa B ligand, suppression of the protein kinase B-Akt/P13K pathway (an intracellular signaling pathway important in regulating cell cycle), vascular endothelial growth factor downregulation, and tumor protein-P53 tumor suppressor upregulation. Conclusions. It is evident that natural extracts have the ability to inhibit cancer progression. Continued research in this field could facilitate the use of natural extracts with currently available anticancer agents. [ABSTRACT FROM AUTHOR]