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Aims: TP53 alterations have a significant prognostic effect in myeloid neoplasms. Our objective was to investigate the TP53 gene mutation status, p53 protein expression and their relationship in dysplasia‐related myeloid neoplasms with varying levels of myeloblast counts. Methods and results: A total of 76 bone marrow biopsy samples with different blast counts were analysed. Total and strong (3+) p53 expression was determined. Dual immunohistochemical staining was performed to determine the cell population associated with p53 expression. NGS analysis was performed using the Accel‐Amplicon Comprehensive TP53 panel. Both p53 expression and TP53 VAF showed a significant correlation with the myeloblast ratio (P < 0.0001); however, p53 expression was also present in other cell lineages. The VAF value exhibited a significant correlation with p53 expression. A high specificity (0.9800) was observed for TP53 mutation using the ≥ 10% strong (3+) p53 cut‐off value, although the sensitivity (0.4231) was low. Conclusions: Strong (3+) p53 expression using a ≥ 10% cut‐off value accurately predicts TP53 mutation but does not reveal the allelic state. The p53 expression is significantly influenced by myeloblast count, and histological interpretation should consider the presence of intermixed non‐neoplastic marrow cells with varying physiological p53 expression. [ABSTRACT FROM AUTHOR]

Colorectal Cancer (CRC) is a global medical problem that has a high rate of mortality. Interestingly, evaluating the hematopoietic growth factors is useful in the early diagnosis of CRC. Henceforth, this study was designed to measure the potential role of Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Interleukin 3 (IL-3) in CRC progress and their relation to P53 expression and global DNA methylation (5mC). Blood samples were collected from a total of 60 Iraqi patients who participated in this study and were diagnosed with CRC, and from 30 healthy volunteers who served as control for comparison purposes. Serum levels of GM-CSF and IL-3 were assessed quantitatively using enzyme linked immunosorbent assay (ELISA). Also, DNA and RNA were extracted from the whole blood samples and DNA methylation and gene expression of P53 were estimated. There were significant differences in the serum levels of GM-CSF and IL-3 between CRC patients and controls. Also, a positive link between serum GMCSF and IL-3 was detected. Regarding demographic characteristics of the patients (age, gender and CRC status) and GM-CSF, IL-3 were found to have statistically highly significant differences (P≤0.001). No significant correlation was found between levels of P53 expression, global DNA methylation between hematopoietic growth factors as immune modulators. The differences of GM-CSF and IL-3 at serum levels may be used as useful biomarkers for CRC progression. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia, a potentially precancerous lesion primarily attributed to tobacco use, poses a significant health concern worldwide. Identifying reliable prognostic markers for predicting the malignant transformation of oral leukoplakia is essential for early intervention and improved patient outcomes. This study explores the use of tissue p53 expression as a potential prognostic marker for assessing the risk of malignant transformation in individuals with tobacco-induced oral leukoplakia. Materials and Methods: In this retrospective cohort study, tissue samples from 150 patients with tobacco-induced oral leukoplakia were collected and analyzed for p53 expression using immunohistochemistry. Clinical data, including age, gender, tobacco consumption history, and follow-up information, were also gathered. Patients were categorized into two groups based on p53 expression: high p53 and low p53. The follow-up period ranged from 2 to 5 years. Results: Among the 150 patients, 65 (43.3%) exhibited high p53 expression in their oral leukoplakia tissue samples, while the remaining 85 (56.7%) had low p53 expression. During the follow-up period, 20 out of 65 patients (30.8%) with high p53 expression experienced malignant transformation, whereas only 8 out of 85 patients (9.4%) with low p53 expression developed malignancies. The odds ratio for malignant transformation in the high p53 group compared to the low p53 group was 4.12 (95% CI: 1.79-9.47, p < 0.001). Conclusion: This study demonstrates that tissue p53 expression is a valuable prognostic marker for assessing the risk of malignant transformation in individuals with tobacco-induced oral leukoplakia. Patients with high p53 expression in their oral lesions are significantly more likely to experience malignant transformation compared to those with low p53 expression. These findings underscore the importance of regular monitoring and early intervention for individuals with high p53 expression to reduce the risk of oral cancer development. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is an extensively used plasticizer and being non-covalently bound to plastics it leaches out into the environment. This addresses a grave concern on its potential human exposure and subsequent deleterious effects. The ameliorative potential of Spirulina (Arthrospira platensis) against DEHP-induced toxicity was assessed in rats. Group I was control. Group II and III, were exposed to a low dose of DEHP (125 mg/kg), and Group IV and V were exposed to a high dose of DEHP (250 mg/kg). Group III and V were treated with spirulina orally (1000 mg/Kg) for 3 weeks. Exposure to DEHP elicited marked oxidative stress and associated DNA damage in a dose-dependent manner. The hepatic expression of p53 was also significantly suppressed. Liver and kidney function tests showed marked alterations. Treatment with spirulina efficaciously reversed the adverse effects. Thus, these findings offer a nutritional intervention of spirulina to combat the environmental exposure to plasticizers. [ABSTRACT FROM AUTHOR]

[Display omitted] • The charatrization was done by UV-Vis, FE-SEM and FT-IR. • The nanopariicles indicated the therapeutic effects. • The nanopariicles indicated the antioxidant effects. This research details the synthesis of biogenic silver nanoparticles utilizing Origanum majorana as a supporting material. The leaves of the plant served as a natural reducing agent and a proficient stabilizer for the generated silver nanoparticles (Ag NPs). The formulated NPs were analyzed through the analysis of their physicochemical properties utilizing UV–Vis, FT-IR, and FE-SEM techniques. The investigation of the antioxidant characteristics of the Ag NPs was followed using the DPPH assay. The results revealed that the silver nanoparticles exhibited considerable antioxidant activity, as evidenced by the IC 50 value. Recent findings suggest that the effectiveness of nanoparticles in treating human breast cancer can be linked to their antioxidant characteristics. An evaluation was followed on the ability of biologically synthesized Ag NPs to combat breast cancer in various cell lines. The silver nanoparticles exhibited significant anti-breast cancer properties, successfully eradicating the MCF10 cancer cell line in a manner that was influenced by both time and concentration, as assessed through the MTT assay. Ag NPs facilitate cell apoptosis, a process linked to elevated levels of pro-apoptotic markers, including Bax and cleaved caspase-8, while concurrently reducing the concentration of the anti-apoptotic marker Bcl-2. Furthermore, silver nanoparticles exhibit a decrease in colony formation in comparison to the respective control group. The examination of molecular pathways in cells exposed to Ag NPs revealed a significant elevation in p53 expression, coupled with a decrease in both total and phosphorylated levels of Signal Transducer and Activator of Transcription 3 (STAT3) in the studied cell lines. This suggests that p53 and STAT3 play essential roles in the biological responses triggered by the extract in human breast cancer cells. [ABSTRACT FROM AUTHOR]

Simple Summary: The addition of chromosome 17 polysomy/HER2 amplification status to the updated EAU and AUA scores improves their accuracy, allowing molecular reclassification of EAU high-risk NMIBCs and G2 tumors. Based on this, we propose to reclassify the non-HER2 amplified, non-polysomic EAU 3–4 (high- and very high-risk) cases to the EAU 2 (intermediate) risk group to prevent unnecessarily strict follow-up and treatment for these patients. Furthermore, to classify Chr17 polysomic and/or HER2 amplified G2 tumors as high-grade (HG) and non-HER2 amplified, non-polysomic G2 tumors as low-grade (LG) NMIBCs (G1 and G3 tumors remain graded as low- and high-grade, respectively). Thus, the implementation of Chr17 polysomy/HER2 amplification testing would provide an immediate and simple solution to further refine the prognostic risk assessment of NMIBCs in the uro-oncology practice. Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) significantly worsens life expectancy. Its risk can be assessed by clinicopathological factors according to international guidelines. However, additional molecular markers are needed to refine and improve the prediction. Therefore, in the present study, we aimed to predict the progression of NMIBCs to MIBC by assessing p53 expression, polysomy of chromosome 17 (Chr17) and HER2 status in the tissue specimens of the tumors of 90 NMIBC patients. Median follow-up was 77 months (range 2–158). Patients with Chr17 polysomy or HER2 gene amplification had a higher rate of disease progression (hazard ratio: 7.44; p < 0.001 and 4.04; p = 0.033, respectively; univariate Cox regression). Multivariable Cox regression models demonstrated that the addition of either Chr17 polysomy or HER2 gene amplification status to the European Association of Urology (EAU) progression risk score increases the c-index (from 0.741/EAU/ to 0.793 and 0.755, respectively), indicating that Chr17 polysomy/HER2 amplification status information improves the accuracy of the EAU risk table in predicting disease progression. HER2/Chr17 in situ hybridization can be used to select non-progressive cases not requiring strict follow-up, by reclassifying non-HER2-amplified, non-polysomic NMIBCs from the high- and very high-risk groups of EAU to the intermediate-risk group. [ABSTRACT FROM AUTHOR]

Abstract Background The study investigated the expression and the clinicopathological significance of p53, p27, Ki-67, E-cadherin, and HER2 in upper urinary tract urothelial carcinomas (UTUC) from Tunisian patients. We performed a retrospective study of 66 UTUC. Main clinicopathological features were reported. The expression of p53, p27, Ki-67, E-cadherin, and HER2 was investigated by immunohistochemistry on whole tissue section. Results Expression of p53, Ki-67, p27, E-cadherin, and HERE2 was reported in 36.4%, 69.7%, 90.9%, 100%, and 0% of cases, respectively. p53 expression was associated with stage (p = 0.001), positive surgical margin (p = 0.005), and shorter recurrence-free survival (RFS; Log Rank test, p = 0.026). Ki-67 and p27 expression was associated with stage (p < 0.001 and p = 0.001, respectively) and grade (p < 0.001 and p = 0.001, respectively). Using Kaplan-Meier test, the positive surgical margin was associated with shorter RFS compared to free surgical margin (Log Rank test, p = 0.031). Moreover, in univariate Cox regression analysis, surgical margin (p = 0.041; HR 0.325, 95% CI 0.110–0.956) and p53 expression (p = 0.035; HR 0.328, 95% CI 0.116–0.925) were the significant factors associated with RFS. Conclusions Together, our findings suggest that positive surgical margin and p53 expression were potential prognostic factors of UTUC since both were associated with shorter RFS in Tunisian patients.

Abstract Background Algae being one of the dominant organisms in nature can provide best opportunity for the discovery of new anti-cancer drugs. The aim of the present study was to investigate the anti-cancer and anti-angiogenic potential of the brown marine alga Chnoospora minima. Result The methanol extract of C. minima and its bioactive fraction (CF4) have highly significant cytotoxic effects to HepG2, HeLa and MCF-7 cancer cell lines. The fraction’s ability to induce apoptosis in the cancer cells was evidenced by increased caspase activity (caspase-3, 7 and 10), DNA fragmentation pattern and upregulated expressions of Bax and p53 genes. The bioactive fraction was not toxic to human peripheral lymphocytes. HPLC, ESI-MS and GC-MS analysis of CF4 fraction indicated the presence of the compound hexadecanoic acid which might be responsible for the observed anti-cancer activity of C. minima. The methanol extract of C. minima exhibited anti-angiogenic effects on chick embryos. Conclusion It can be concluded that fraction, CF4, from C. minima is a promising source of an anti-cancer lead molecule.

Medulloblastoma (MB) is a common malignant intracranial neoplasms in children. The treatment and prognosis of this tumor depends on histology and molecular subtypes. Survivin, implicated in various malignancies, may hold prognostic significance. We investigated survivin and p53 immunoreactivity in different histological subtypes in 20 MB cases from January 2018 to June 2021. Immunohistochemistry revealed survivin expression in 75% (15/20) of cases, with cytoplasmic (10 cases), nuclear (four cases), or combined expression (one case). p53 nuclear expression was present in 35% (7/20) of cases. Classical variant MB exhibited predominant p53 and cytoplasmic survivin expression. Given the association of survivin and p53 expression with poor prognosis, especially in the prevalent classical variant, targeted therapies may hold promise for MB treatment advancement., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, All India Institute of Medical Sciences, Patna, India issued approval AIIMS/Pat/IEC/PGTH/July19/34. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, G et al.)

Aims: The aim of this study was to characterise grade 1 (G1) endometrioid carcinoma in the elderly, by using clinicopathological features and immunohistochemical features of surrogate markers of molecular subtypes. Methods and results: We retrospectively analysed tumour samples from 268 patients with G1 endometrioid carcinoma (<40 years, n = 24; 40–59 years, n = 169; ≥60 years, n = 75) for whom long‐term clinical follow‐up data were available. G1 endometrioid carcinoma in the elderly (≥60 years) was characterised by frequent deep myometrial invasion, less frequent endometrioid intraepithelial neoplasia (EIN), lack of benign hyperplasia (BH), less frequent squamous differentiation, and occasional aberrant p53 expression. In contrast, this condition in the young (<40 years) was characterised by frequent EIN, BH, and squamous differentiation. Univariate analysis revealed that elderly status (≥60 years), International Federation of Obstetrics and Gynecology (FIGO) 2009 stage and aberrant p53 expression were significantly associated with shorter progression‐free survival, and multivariate analysis revealed that elderly status and FIGO 2009 stage were independently associated with a poor prognosis. Conclusions: G1 endometrioid carcinoma in the elderly is more aggressive than that in the young, and elderly status is an independent predictor of shorter progression‐free survival in this condition. We propose that type 1 tumours can be subdivided into type 1a (young age at onset and indolent) and type 1b (old age at onset and relatively aggressive). [ABSTRACT FROM AUTHOR]

The therapeutic effectiveness of anticancer drugs with a selective target for the nucleus of cancer cells may be improved by experimental approaches. In this regard, the formulation of anticancer drugs is considered one of the best ways to improve their effectiveness in targeting cancerous tissues. To enhance the anticancer activity of 2-methoxy-estradiol (2 ME) for breast cancer, 2-methoxyestradiol loaded alpha lipoic acid nanoparticles have been formulated. The prepared formula was observed to be spherical with a nanometer-scale and low PDI size (.234). The entrapment efficiency of the 2ME-ALA NPs was 87.32 ± 2.21% with > 85% release of 2 ME within 24 h. There was a 1.2-fold increase in apoptosis and a 3.46-fold increase in necrosis of the MCF-7 cells when incubated with 2ME-ALA NPs when compared to control cells. This increased apoptosis was also associated with increased ROS and increased p53 expression in 2ME-ALA NPs treated cells compared to the raw-2 ME group. Evaluation of cell-cycle data showed a substantial arrest of the G2-M phase of the MCF-7 cells when incubated with 2ME-ALA NPs. At the same time, a dramatically increased number of pre-G1 cells showed the increased apoptotic potential of the 2 ME when administered via the proposed formulation. In the end, the differential upregulation of caspase-3, p53, and ROS in MCF-7 cells established the superiority of the 2ME-ALA-Ms approach in targeting breast cancer. In summary, these results demonstrate that 2ME-ALA NPs are an efficient delivery tool for controlling the growth of breast cancer cells. [ABSTRACT FROM AUTHOR]

Introduction: Overexpression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and p53 are the postulated aetiopathogenesis in pterygium. VEGF is responsible for the induction of COX-2 expression, whereas p53 plays an important role in the regulation of VEGF. This study aimed to evaluate the immunohistochemistry of COX-2 and p53 expressions from excised pterygium tissue from patients who received intralesional ranibizumab (anti-VEGF) injection 2 weeks prior to pterygium surgery.Materials and Methods: An interventional comparative study involving patients presenting with primary pterygium was conducted between September 2015 and November 2017. The patients were randomized into either the intervention or control group. Patients in the intervention group were injected with intralesional ranibizumab (0.5 mg/0.05 ml) 2 weeks prior to surgery. Both groups underwent pterygium excision followed by conjunctival autograft. Immunohistochemistry staining was performed to evaluate COX-2 and p53 expressions in the excised pterygium tissue.Results: A total of 50 patients (25 in both the intervention and control groups) were recruited. There were 34 (68%) patients with grade III pterygium and 16 (32%) patients with grade IV pterygium. There was statistically significant difference in reduction of COX-2 expression in the epithelial layer [84.0% (95% CI: 63.9, 95.5)] (p = 0.007) and stromal layer [84.0% (95% CI: 63.9, 95.5)] (p < 0.001) between intervention and control groups. There was no significant difference in the reduction of p53 expression between the two groups.Conclusion: This study demonstrated the possible use of intralesional anti-VEGF treatment prior to pterygium excision as a potential future modality of adjunctive therapy for pterygium surgery.

Objective(s): The significant contribution of nanoparticles to cancer treatment has attracted therapeutic attention. The present study aimed to evaluate the synergistic effects of 5-fluorouracil (5-FU) and zinc oxide nanoparticles (ZnO NPs) as multimodal drug delivery on human breast cancer MCF-7 cells.Materials and Methods: In this in-vitro study, the impact of 5-FU and ZnO NPs in the single or combined forms was evaluated on cell viability, colony formation, apoptosis, p53 gene expression, and Bcl-2 signaling protein in MCF-7 breast cancer cell line using several techniques, such as MTT, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot.Results: In this study, 5-FU combined with ZnO NPs showed synergistic effects against MCF-7 within 48 hours. In addition, the combination of 5-FU and ZnO NPs at the respective concentrations of 1 µM and 45 µg/ml exhibited significant apoptosis (79.53%), p53 gene expression (3.6 folds), reduction of cell invasion (9.82%), and plating efficiency (5%), thereby leading to the significant reduction of cell viability (40±0.9%) and decreased Bcl-2 anti-apoptotic protein relative to untreated control cells. Conclusion: According to the results, the synergistic effects of combined ZnO NPs and 5-FU on MCF-7 human breast cancer cells were exerted via Bcl-2 inhibition and the up-regulation of p53 expression.

Objective: Mutations in TP53 lead to loss of function (LOF) or gain of function (GOF) of the corresponding protein p53 and produce a different effect on the tumor. Our goal was to determine the spectrum of somatic TP53 variants in BRCA1/2 associated high-grade serous ovarian cancer (HGSOC).Methods: The population under study comprised of HGSOCs with pathogenic variants in BRCA1 (n = 78) or BRCA2 (n = 21). Only chemo-naive and platinum-sensitive patients were included in this study. The case group of the IARC database (n = 1249) with HGSOC not stratified by BRCA status was used as a reference. A custom NGS panel was used for sequencing TP53 and mutational hot-spots of other genes, and p53 expression was evaluated by immunohistochemistry for 68 cases of HGSOCs.Results: Somatic TP53 variants (95) or inhibition of wild-type p53 expression (3) were observed in 98 cases. The sample with normal p53 had CDKNA1 variants. The frequency of truncating variants was significantly higher than in the reference cohort (30.3 vs. 21.0%, p = 0.01). Most of the samples (41/68) demonstrated low (or absent) expression of p53, and 17 samples overexpressed p53. LOH was typical for TP53 nonsense variants (14/15). In total, 68/95 samples were LOH positive and showed LOH in all tumorous cells, thus indicating the driver effect of TP53 mutations. Three specimens had KRAS, BAX, APC, and CTNNB1 subclones variants.Conclusion: High frequency of TP53 truncating variants, the low expression of mutant p53, and low incidence of oncogene mutations show potential GOF properties of p53 to be poorly represented in BRCA1/2 associated HGSOC.

The p53 protein is one of the transcription factors responsible for cell cycle regulation and prevention of cancer development. Its expression is regulated at the transcriptional, translational and post-translational levels. Recent years of research have shown that the 5ʹ terminus of p53 mRNA plays an important role in this regulation. This region seems to be a docking platform for proteins involved in p53 expression, particularly under stress conditions. Here, we applied RNA-centric affinity chromatography to search for proteins that bind to the 5ʹ terminus of p53 mRNA and thus may be able to regulate the p53 expression profile. We found heterogeneous nuclear ribonucleoprotein K, hnRNP K, to be one of the top candidates. Binding of hnRNP K to the 5ʹ-terminal region of p53 mRNA was confirmed in vitro. We demonstrated that changes in the hnRNP K level in the cell strongly affected the p53 expression profile under various stress conditions. Downregulation or overexpression of hnRNP K caused a decrease or an increase in the p53 mRNA amount, respectively, pointing to the transcriptional mode of expression regulation. However, when hnRNP K was overexpressed under endoplasmic reticulum stress and the p53 amount has elevated no changes in the p53 mRNA level were detected suggesting translational regulation of p53 expression. Our findings have shown that hnRNP K is not only a mutual partner of p53 in the transcriptional activation of target genes under stress conditions but it also acts as a regulator of p53 expression at the transcriptional and potentially translational levels. [ABSTRACT FROM AUTHOR]

Objective: Mutations in TP53 lead to loss of function (LOF) or gain of function (GOF) of the corresponding protein p53 and produce a different effect on the tumor. Our goal was to determine the spectrum of somatic TP53 variants in BRCA1/2 associated high-grade serous ovarian cancer (HGSOC). Methods: The population under study comprised of HGSOCs with pathogenic variants in BRCA1 (n = 78) or BRCA2 (n = 21). Only chemo-naive and platinum-sensitive patients were included in this study. The case group of the IARC database (n = 1249) with HGSOC not stratified by BRCA status was used as a reference. A custom NGS panel was used for sequencing TP53 and mutational hot-spots of other genes, and p53 expression was evaluated by immunohistochemistry for 68 cases of HGSOCs. Results: Somatic TP53 variants (95) or inhibition of wild-type p53 expression (3) were observed in 98 cases. The sample with normal p53 had CDKNA1 variants. The frequency of truncating variants was significantly higher than in the reference cohort (30.3 vs. 21.0%, p = 0.01). Most of the samples (41/68) demonstrated low (or absent) expression of p53, and 17 samples overexpressed p53. LOH was typical for TP53 nonsense variants (14/15). In total, 68/95 samples were LOH positive and showed LOH in all tumorous cells, thus indicating the driver effect of TP53 mutations. Three specimens had KRAS, BAX, APC , and CTNNB1 subclones variants. Conclusion: High frequency of TP53 truncating variants, the low expression of mutant p53, and low incidence of oncogene mutations show potential GOF properties of p53 to be poorly represented in BRCA1/2 associated HGSOC. [ABSTRACT FROM AUTHOR]

Breast cancer is a disease that specifically affects women, but it may affect the P53 gene, the gene responsible for blocking tumors. Breast cancer is a cancer that forms in breast cells. Breast cancer comes after skin cancer in that it is the most common type of cancer among women and may affect breast cancer for both men and women, but more common in women. Significant support for breast cancer awareness and research funding has made progress in the diagnosis and treatment of breast cancer. Survival rates for breast cancer patients increased, and the number of deaths related to this disease decreased regularly, due in large part to a number of factors, such as early detection, the use of a new treatment method that takes into account the individual case, and a better understanding of the nature of this disease. Relationships between fibronectin and the expression P53 of the study group that were invariably studied based on Pearson's relationship as a display, there was a strong correlation between the studied mark (p ≥ 0.05), and at the same time a strong correlation between the sample patient section and subject tags (p. 0.05), This means that there is a strong and strong relationship. Any malignant cell needs a different factor for growth and the metabolites are specially assigned to oxygen and nutrition from the vascular system. The sign of the immune system fibronectin and P53 act as a catalyst for the formation of tumor blood vessels for breast cancer tissue. A different study confirmed focus in knowledge of the level of expression of fibronectin and P53marker that were highly related to breast cancer. [ABSTRACT FROM AUTHOR]

Background and objectives: Mutations of the TP53 gene have an unfavorable prognosis in Myelodysplastic Syndromes (MDS). The product of the TP53gene is the p53 protein. Most of TP53mutations entail the accumulation of the protein in the nucleus of tumor cells. The immunohistochemical (IHC) staining for p53 can be a surrogate suggesting a mutational status and, if overexpressed, seems to be of prognostic value by itself. The best prognostic cut-off value of overexpression is controversial. The aim of this pilot study is to investigate about the correct value from a homogenous group of patients with higher IPSS-R risk MDS. Methods: In sixty consecutive patients diagnosed with MDS and categorized as IPSS-R risk “intermediate”, “high” and “very high”, the bone marrow biopsies performed at the diagnosis were retrospectively re-examined for IHC p53 expression. The result of p53 expression was subsequently related to survival. Results: A worst overall survival was observed both in patients whose IHC p53 expression was ≥5% and ≥ 10% compared to the patients with a p53 expression respectively below 5% (p= 0.0063) or 10% (p=0.0038). Conclusions: The ICH p53 expression in bone marrow biopsy in higher risk MDS was confirmed to have prognostic value. These results indicate more than 10% expression as the best cut off value.

Objective(s): The significant contribution of nanoparticles to cancer treatment has attracted therapeutic attention. The present study aimed to evaluate the synergistic effects of 5-fluorouracil (5-FU) and zinc oxide nanoparticles (ZnO NPs) as multimodal drug delivery on human breast cancer MCF-7 cells. Materials and Methods: In this in-vitro study, the impact of 5-FU and ZnO NPs in the single or combined forms was evaluated on cell viability, colony formation, apoptosis, p53 gene expression, and Bcl-2 signaling protein in MCF-7 breast cancer cell line using several techniques, such as MTT, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot. Results: In this study, 5-FU combined with ZnO NPs showed synergistic effects against MCF-7 within 48 hours. In addition, the combination of 5-FU and ZnO NPs at the respective concentrations of 1 µM and 45 µg/ml exhibited significant apoptosis (79.53%), p53 gene expression (3.6 folds), reduction of cell invasion (9.82%), and plating efficiency (5%), thereby leading to the significant reduction of cell viability (40±0.9%) and decreased Bcl-2 anti-apoptotic protein relative to untreated control cells. Conclusion: According to the results, the synergistic effects of combined ZnO NPs and 5-FU on MCF-7 human breast cancer cells were exerted via Bcl-2 inhibition and the up-regulation of p53 expression. [ABSTRACT FROM AUTHOR]

Aberrant expression of the interleukin-3 receptor alpha chain (IL3RA or CD123) is frequently observed in patients with a subset of leukemic disorders, including acute myeloid leukemia (AML), particularly in leukemia stem cells. We analyzed the relationships between immunohistochemical (IHC) expression, including that of CD123, and clinical outcomes. This study involved a retrospective analysis of 48 patients diagnosed with de novo AML (M0-M5, n = 48) at our hospital between February 2008 and September 2015. Among patients with de novo AML, CD123 expression was associated with a failure to achieve complete response (CR) to initial induction chemotherapy (P = 0.044) and poor overall survival (OS) (P = 0.036). This is the first study using IHC to demonstrate that CD123 expression is associated with a poor CR rate and poor OS in de novo AML patients. These results support previous reports using flow cytometry (FCM). CD123 expression may thus be useful for assessing AML patients' prognoses. At the time of diagnosis, CD123 expression analysis using IHC may represent a clinically useful assessment for de novo AML patients. [ABSTRACT FROM AUTHOR]

Immunohistochemistry studies on p53 inactivation in esophageal cancer are available with inconclusive results. Data on the combined effect of p53 protein accumulation and TP53 genomic deactivation in large scale studies for esophageal cancer are currently lacking. A tissue microarray with 691 esophageal cancer samples was analyzed by p53 immunohistochemistry and fluorescence in situ hybridization (FISH). Nuclear p53 accumulation was observed in 45.9% of patients with adenocarcinoma (AC) and in 40.0% in squamous cell carcinoma (SCC). Heterozygous TP53 deletions occurred in 40.9% in AC and in 19.4% in SCC. Homozygous deletions did not occur at all. High-level p53 immunostaining was associated with shortened overall survival in AC and SCC while TP53 deletions alone showed no correlation with survival. High-level p53 immunostaining in patients with AC was associated with advanced tumor (P=0.019) and Union for International Cancer Control stages (P=0.004), grading (P=0.027) and the resection margin status (P=0.006). Associations between p53 immunostaining and SCC were not found. TP53 deletions were found to be associated with advanced tumor stages (P=0.028) and the presence of lymph node metastasis (P=0.009) in SCC. In conclusion, strong p53 immunostaining, but not TP53 deletion alone, is associated with unfavorable outcomes and may therefore represent a clinically useful molecular marker in esophageal cancer. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are successful for their therapeutic application in immune and inflammatory contexts due to their anti-inflammatory, trophic, and immunomodulatory roles. However, though MSCs have the potential to provide regenerative treatment toward a wide range of devastating diseases, massive cell death of transplanted MSCs remains an obstacle to overcome. The relation between MSCs and inflammation is multifactorial and challenging to comprehend. Fever is a critical component of the inflamed microenvironment. Also, the choice of MSC source could be critical in determining the fate of transplanted cells under stress conditions. Here we investigated the thermosensitivity of Wharton's jelly MSCs (WJ-MSCs) to elevated temperature in the physiological fever range. We explored the effect of febrile range temperature on morphology, viability, proliferation kinetics, and cell cycle status of WJ-MSCs. WJ-MSCs adopted a flattened morphology at 40°C, and our data from proliferation kinetics study using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assays showed that WJ-MSCs had reduced proliferation and viability at 40°C compared with control cultures. There was also a G0/G1 cell cycle arrest, which was further confirmed by messenger RNA (mRNA) levels of genes specific for different stages of cell cycle. On evaluating p53 status, we observed an increase in p53 protein expression and its nuclear localization in WJ-MSCs exposed to 40°C. Its downstream effector p21 too was upregulated. Moreover, this temperature-induced p53 induction was inhibited on exposure to 40°C in the presence of NF-κB pathway inhibitor, pyrrolidinedithiocarbamate (PDTC) or endonuclease-prepared small interfering RNA (esiRNA) targeting p65. Febrile temperature exposure did not affect the senescence status of WJ-MSCs. The MSC-specific surface antigen profile at 40°C was similar to control WJ-MSCs. Our findings suggest that under febrile temperature stress conditions, WJ-MSCs exhibit G0/G1 cell cycle arrest and reduction in viable cell count, while retaining their basic characteristics, with an underlying interplay of p53 and NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background: Mutation of p53 gene is one of the most common events in oral carcinogenesis. Accumulation of p53 protein has also been detected in premalignant lesions.Materials and Methods: This study included 40 biopsy samples, which were received in department of pathology, Sarojini Naidu Medical College, Agra, to ascertain p53 expression by immunohistochemically, in patients with oral squamous cell carcinomas and to correlate its expression with histological grade, different sites in oral cavity and tobacco intake/smoking habits.Results: Out of 40 biopsies of oral mucosa, 03 showed normal oral mucosa and 37 were diagnosed as squamous cell carcinoma (SCC), most patients were in 5th and 6th decade and majority (86.5%) of oral SCC were males with buccal mucosa being the most common site. There was a statistically significant difference in p53 expression between oral SCC and normal oral mucosa (p value Conclusion: Abnormal p53 protein was detected in 64.9% of oral squamous cell carcinoma, but not in normal oral mucosa. p53 expression was associated with malignant transformation of oral mucosa.

Pada karsinoma terjadi peningkatan proliferasi sel dibanding dengan apoptosis sel, sehingga sel akan tumbuh lebih banyak dari jumlah normalnya. Pada kondisi homeostasis, untuk dapat mengatur jumlah sel pada tubuh manusia, mekanisme utama tubuh adalah dengan menghasilkan p53. Protein p53 sebagai protein penghambat tumor mengaktifkan pembentukan p21 yang berperan untuk aktivasi beberapa komplek kinase tergantung siklin dan memutus siklus pembelahan sel. Tujuan penelitian ini untuk analisis hubungan ekspresi p53 terhadap prognosis radioterapi pada karsinoma nasofaring dengan metode retrospektif. Ekspresi p53 telah dicat imunohistokimia dan dianggap positif bila jumlah sel tumor positif lebih dari 10% dan dianalisis hubungan ekspresi p53 dengan prognosis pada pasien karsinoma nasofaring dengan radioterapi. Hasil penelitian menunjukkan dari 43 Pasien karsinoma nasofaring dengan terapi radiasi terdapat 8 orang (18,6%) meninggal selama perawatan. Berdasarkan jenis kelamin, 74,42% pasien adalah laki-laki dan 25,58% wanita. Kelompok usia 51 sd 60 tahun adalah yang terbanyak yaitu sebesar 14 kasus (32,56%). Terdapat hubungan yang bermakna antara ekspresi p53 dengan prognosis hasil terapi radiasi pada karsinoma nasofaring p = 0,000 (p0,05). Disimpulkan bahwa ekspresi p53 yang positif akan memberikan prognosis yang lebih baik terhadap hasil terapi radiasi pada karsinoma nasofaring. In the cancer condition, there is increasing of cell proliferation than apoptosis, so cell will grow rapidly than normal. In normal homeostatic, to set the amount of the cells in human body, the primary body mechanism is producing gene p53. The p53 as protein cancer suppressor activate p21 that role to activate some of complex kinase based on cyclin and cut mitosis cycle. The aims of this research to analyze relation p53 expression with prognosis of radiotherapy in nasofaringeal carcinoma using retrospective method. P53 expression strained by imunohistochemistry and considered positive if we find greater than 10% positif cell tumor then analyzed relation p53 expression with prognosis of radiotherapy in nasofaringeal carcinoma. The result shows from 43 patient nasofaringeal carcinoma with radiotherapy there are 8 patient (18,6%) died. 74,42% patient are male and 25,58% are female. 51-60 years old group is 14 cases (32,56%). There was significant correlation between prognosis and p53 expression p= 0,000 (p0,05). The conclusion is that positive p53 expression will give a better prognostic for nasofaringeal carcinoma with radiotherapy.

P53 is important for cell cycle regulation, and its overexpression is seen in malignant tumors. We examined correlation between p53 expression and cell proliferation, and its role in the pathogenesis of keratinocyte skin tumors. We used biopsies from patients with squamous cell carcinoma, actinic keratosis and keratoacanthoma. We examined crosssections stained with HE and using anti-cytokeratin, antip53 and anti-Ki67 antibodies. Expression of p53 is found in 87, 85% of SCC, in 83. 3% of AK and 13. 4% KA. The high index of p53 expression was higher in SCC and AK compared to KA. We also observed a positive correlation between the expression of p53 and localization of the tumors. The largest proportion of subjects with AK and SCC has a high index of p53 expression on photoexposed region. We also observed that p53 expression correlates with age whereby in AK p53 expression increases with age. The high index of proliferation is most frequent in SCC and KA. Also at AK we found a strong correlation between a moderate proliferation index and tumor localization in photoexposed region. Between the proliferation index and p53 expression we observed a significant positive correlation only in SCC. Proliferation index and the expression of p53 are useful for the differentiation of precursor keratinocyte lesions and skin carcinoma. High p53 expression has been associated with the aging and significantly correlates with the exposure to UV radiation in SCC and AK. High expression of p53 in AK and SCC supports the importance of this oncoprotein in carcinogenesis of the skin. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is associated with a high relapse rate and is the fifth leading cause of cancer deaths in women. The genetic profile of a tumor is responsible for deciding response to chemotherapeutic agents. In this study, we investigate the relation between survivin and p53 expression and response to chemotherapeutic agents of primary cultures of ovarian cancer cells established from ascitic fluid. Materials and Method: Ascitic fluid and Dulbecco’s modified Eagle medium was mixed in equal proportion in culture flasks and incubated to establish primary culture. The cells were treated with different combinations of carboplatin and paclitaxel with and without survivin small interfering RNA transfection. Cell survival was estimated by MTT assay. Survivin and p53 expression was quantified by real-time polymerase chain reaction. Results: Out of 19 ascitic fluid samples, 13 primary cultures of ovarian cancer cells were established. The half maximal inhibitory concentration doses of carboplatin (≥70 μg/mL) and paclitaxel (≥18 μg/mL) were high for 10/13 and 5/13 patients, respectively. Survivin messenger RNA expression was significantly downregulated on treatment with carboplatin (100 μg/mL), paclitaxel (12.5 μg/mL), and a combination of carboplatin (50 μg/mL) and paclitaxel (6.25 μg/mL). Only paclitaxel-treated ovarian cancer cells showed decrease in expression of p53. Survivin small interfering RNA increased sensitivity of the primary cultures to chemotherapeutic agents. Conclusions: The present study highlights the fact that establishing primary cultures from ascitic fluid may help to develop personalized treatment regime for individual patients based on their molecular profile. Our study also shows that supplementing taxols drugs with survivin inhibitors may prove to be beneficial in the treatment of ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Background: p53 acts as a transcription factor to regulate the expression of genes that modulate various cellular activities. The proliferation of cancer cells has been inhibited under the exposure to low-intensity (18 peak-to-peak voltage) and intermediate-frequency (100 KHz) electric fields generated between 2 capacitive electrodes. Therefore, the aims of this study were to observe the molecular mechanism of cell death caused by noncontact electric field exposure and to determine whether p53 protein can serve as a biomarker for this exposure or not. Methods: Oral squamous cell carcinoma, HeLa, and bone marrow mesenchyme cells were exposed to noncontact electric fields of Electro-Capacitive Cancer Therapy (ECCT) for 24 h. To observe the mechanism of cell death caused by ECCT, immunocytochemistry of p53 was performed, and the p53 expression was evaluated using immunoreactive score (IRS) calculation. Results: Electric field exposure by ECCT increased the percentage of dead cells in oral cancer cells (18.39%), HeLa cells (6.60%), and bone marrow mesenchyme cells (34.05%) with statistical significance using the independent t test compared to each control group. The IRS of p53 in oral cancer, HeLa, and bone marrow mesenchyme cultures were 10.50, 11.25, and 4.94, respectively. Conclusion: The high IRS shown in the treated oral cancer and HeLa culture cells may suggest that p53 expression in these culture cells is associated with the cell death mechanism induced by the exposure to noncontact electric fields, and the increased cell death in these culture cells may correlate with the IRS. [ABSTRACT FROM AUTHOR]

Background: Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterized by abnormal trophoblast tissue. Molar and non-molar hydropic placental changes are the most common forms of GTD. Differential diagnosis of GTD is sometimes problematic. Recently, p53 expression was identified as a good marker for distinguishing GTD types. Aims: Comparison of p53 expression in partial hydatidiform mole (PHM) and hydropic abortion. Methods: In this prospective cross-sectional study, molar and non-molar hydropic pregnancy specimens were collected. Immunohistochemical staining, based on the Labeled Streptavidin Biotin (LSAB) technique, was carried out on multiple 4 mm paraffin block sections prepared from formalin-fixed trophoblastic tissues. Polymer-based Envision was used to assess p53 tumor suppressor protein immunoreactivity. p53 expression was then compared between both groups. Results: In the study, 40 patients were included: 20 with confirmed PHM and 20 with hydropic pregnancy. p53 protein was positive in 60% of patients with PHM and 25% of patients with hydropic pregnancy. The p53 positive rate was significantly higher in patients with PHM ( p = 0.027). Moreover, patients with PHM had a significantly high grade of staining ( p<0.001). Conclusion: Our findings indicate that immunohistochemical analysis of p53 protein can be used to distinguish PHM and hydropic pregnancy. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the association of p53 expression levels with clinicopathological features and prognosis of patients with colon cancer following surgery. The present study included 484 patients with colon cancer that underwent colon resection between December 2003 and December 2011. All follow-ups were censored in December 2013 with a median follow-up time of 43 months. Kaplan-Meier survival curves and Cox regression analysis were used to determine predictors for overall survival rate. p53 expression status (positive or negative) was significantly different between patient groups when categorized by age distribution, disease course, tumor location, maximum tumor diameter, depth of tumor invasion, Dukes' stage, distant metastasis and lymph node (LN) metastasis (P<0.05). Cox regression analysis revealed that age, surgery type, histological subtypes, tumor size, tumor location, LN metastasis, distant metastases, Dukes' stage and p53 expression status are independent factors influencing the survival rate of patients with colon cancer following surgery (P<0.05). Therefore, the present study revealed that the loss of p53 expression levels in tumors was associated with aggressive clinicopathological characteristics in patients with colon cancer. [ABSTRACT FROM AUTHOR]

The development and the synthesis of cationic platinum(II) complexes were realized and their cytotoxic activity was tested on triple negative breast cancer MDA-MB-231 cell line and in two cell lines poorly responsive to cisplatin (DLD-1 and MCF-7). The complex 2c resulted the most potent cytotoxic agent in MDA-MB-231 (IC 50 = 61.9 µM) and more effective than cisplatin on both DLD-1 (IC 50 = 57.4 µM) and MCF-7 (IC 50 = 79.9 µM) cell lines. 2c showed different cellular uptake and pharmacodynamic properties than cisplatin, interfering with the progression of the M phase of the cell cycle. Thus, 2c represents a lead compound of a new class of cytotoxic agents with promising antitumor activity. [ABSTRACT FROM AUTHOR]

Cancer chemotherapeutic drugs can potentially cause several adverse effects that influence a patient's general well-being. Sorafenib, an approved drug used in clinics against multiple cancers whose overall efficacy suffered a serious setback due to various side effects, leading to its frequent discontinuation. Lupeol has recently been considered an important prospective therapeutic agent due to its low toxicity and enhanced biological efficacy. Hence, our study aimed to evaluate whether Lupeol can perturb the Sorafenib-induced toxicity. To test our hypothesis, we studied DNA interaction, level of cytokines, LFT/RFT, oxidant/antioxidant status, and their influences on genetic, cellular, and histopathological changes using both in vitro and in vivo models. The Sorafenib-treated group showed a marked increase in reactive oxygen and nitrogen species (ROS/RNS), an increase in liver and renal function marker enzymes, serum cytokines (IL-6, TNF-α, IL-1β) macromolecular damages (protein, lipid, and DNA), and a decrease in antioxidant enzymes (SOD, CAT, TrxR, GPx, GST). Moreover, Sorafenib-induced oxidative stress caused marked cytoarchitectural damage in the liver and kidney and increased p53 and BAX expression. Interestingly, combining Lupeol with Sorafenib improves all the examined toxic insults caused by Sorafenib. In conclusion, our findings suggest that Lupeol can be used in combination with Sorafenib to reduce ROS/RNS-induced macromolecule damage, which might result in hepato-renal toxicity. This study presents the possible protective effect of Lupeol against Sorafenib-induced adverse effects by perturbing redox homeostasis imbalance and apoptosis leading to tissue damage. This study is a fascinating finding that warrants further in-depth preclinical and clinical studies. • Cancer drug-induced toxicity is a major complication for patients. • Sorafenib-cancer drug used in clinics, showed adverse effects via redox imbalance. • Lupeol - a triterpene successfully restores the anti-oxidant protective machinery. • Lupeol also compensates Sorafenib-induced hepato-renal adverse effects. [ABSTRACT FROM AUTHOR]