Evaluation Of P53 Expression Research Articles

Hypericin Exerts Detrimental Effect on Huh-7 As a Delegacy of Hepatocellular Carcinoma: A P53 Dependent Pathway.

Background: Hepatocellular carcinoma is the most common type of liver cancer which arises from the main cells in the liver. We address many studies investigating anti-cancer role of hypericin, however the proposing corresponding molecular pathway seems to be still a debate. Therefore, the present study aimed to evaluate the apoptotic effect of hypericin on the Huh7 as the liver cancer cell line and its relation with the gate keeper gene P53. Materials and Methods: In this study, the Huh7 cell line and fibroblast cells (as control group) were treated with different concentrations of hypericin for 24 and 48 hours. Detection of cell death was performed by MTT assay and flow cytometry. The expression of bax, bcl2 and p53 mRNAs was evaluated by Real-time PCR. Also, Immunocytochemistry (ICC) analysis was used for further evaluation of P53expression. Results: The results showed that hypericin has a dose-dependent cytotoxic effect on the Huh7 cell line, with no or marginal effect on fibroblastic cells. According to flow cytometry results, about 53%cells underwent apoptosis after exposure to LD50 of hypericin for 24 hours. Real-time PCR data demonstrated that the pro-apoptotic genes Bax and P53 expression level increased. Expectedly ICC results confirmed the up-regulation of P53 proteins in treated samples. Conclusion: Our results indicate the cytotoxicity of hypericin on Huh7 cells by affecting the expression of the gate keeper gene P53; furthermore it is suggested that this herb can be utilized simultaneously with modalities targeting P53 up-regulation or related molecular pathways.

Hypericin Exerts Detrimental Effect on Huh-7 As a Delegacy of Hepatocellular Carcinoma: A P53 Dependent Pathway

Background: Hepatocellular carcinoma is the most common type of liver cancer which arises from the main cells in the liver. We address many studies investigating anti-cancer role of hypericin, however the proposing corresponding molecular pathway seems to be still a debate. Therefore, the present study aimed to evaluate the apoptotic effect of hypericin on the Huh7 as the liver cancer cell line and its relation with the gate keeper gene P53. Materials and Methods: In this study, the Huh7 cell line and fibroblast cells (as control group) were treated with different concentrations of hypericin for 24 and 48 hours. Detection of cell death was performed by MTT assay and flow cytometry. The expression of bax, bcl2 and p53 mRNAs was evaluated by Real-time PCR. Also, Immunocytochemistry (ICC) analysis was used for further evaluation of P53expression. Results: The results showed that hypericin has a dose-dependent cytotoxic effect on the Huh7 cell line, with no or marginal effect on fibroblastic cells. According to flow cytometry results, about 53%cells underwent apoptosis after exposure to LD50 of hypericin for 24 hours. Real-time PCR data demonstrated that the pro-apoptotic genes Bax and P53 expression level increased. Expectedly ICC results confirmed the up-regulation of P53 proteins in treated samples. Conclusion: Our results indicate the cytotoxicity of hypericin on Huh7 cells by affecting the expression of the gate keeper gene P53; furthermore it is suggested that this herb can be utilized simultaneously with modalities targeting P53 up-regulation or related molecular pathways. [GMJ.2020;9:e1896]

Evaluation of p53 expression among Colorectal Cancer patients

Evaluation of p53 expression among Colorectal Cancer patients

Comparison of P53 Intensity, Frequency and Size in Normal Skin Periphery of Squamous Cell Carcinoma, Basal Cell Carcinoma And Melanocytic Nevus in Persian Skin Type

Non-Melanoma Skin Cancer (NMSC), the most prevalent types being Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC), is the most common type of malignancy in human beings. These neoplasms are more frequent in the elderly and fair skinned people and mainly occur on sun-exposed sites of the body. Ultraviolet B (UVB) has a well-known effect in induction and promotion of growth of these cancers. The p53 tumor suppressor gene is believed to be an early target in UV-induced skin carcinogenesis. Aggregates of keratinocytes with p53 protein overexpression are frequently identified in normal human skin and are more prevalent in chronically sun-exposed skin, and have been proposed to play a role in skin cancer pathogenesis. The aim of this study was to clarify the potential role of P53 in the development of NMSC. Immunohistochemical evaluation of p53 expression in peri-lesional skin of 90 cases of SCC, BCC and melanocytic nevi was performed. The well-delineated compact type of p53 clone, but not the strong dispersed type, was significantly more predominant in SCCs in comparison with BCCs and melanocytic nevi (P value=0.001). The size of p53 clones was also significantly greater in SCCs compared to the BCCs (P=0.003) and melanocytic nevi (P=0.001). There was no significant difference between these neoplasms regarding the frequency of P53 clones (P=0.86). This study suggests the possible relationship of epidermal p53 clones with the pathogenesis of SCC.

ORAL SQUAMOUS PAPILLOMA AND SQUAMOUS CELL CARCINOMA

Objectives: The objective of this study was to determine the diagnostic utility ofp53 in differentiating oral squamous papilloma and squamous cell carcinoma. Study Design:A cross-sectional study. Setting: Pathology Department of Shaukat Khanum Memorial CancerHospital and Research Center Lahore. Period: Six months (6-10-10 to 6-04-11). Patients andMethods: A total of 100 oral biopsies fulfilling the inclusion criteria were collected. The expressionof P53 was observed in biopsies of squamous papilloma and squamous cell carcinoma. Datawas entered and analyzed on SPSS version 20 and was analyzed in same package. Sensitivity,specificity, positive predictive and negative predictive values were calculated along theirconfidence intervals at 95% level. Results: One hundred oral lesions were studied, of which 90cases were of squamous cell carcinoma and 10 cases were of squamous papilloma. Majorityof the patients were male (60%). Mean age was 46 years. P53 IHC stain had sensitivity of 92%and specificity of 80% and diagnostic utility of 91% in lesions of squamous cell carcinoma.Conclusion: P53 is positively expressed in oral squamous cell carcinoma and is negativein squamous papilloma. Hence evaluation of p53 expression can be a useful adjunct in thediagnosis of squamous cell carcinoma, especially in cases where it is difficult to distinguishbetween these two entities on morphological grounds.

English

Objectives: The objective of this study was to determine the diagnostic utility ofp53 in differentiating oral squamous papilloma and squamous cell carcinoma. Study Design:A cross-sectional study. Setting: Pathology Department of Shaukat Khanum Memorial CancerHospital and Research Center Lahore. Period: Six months (6-10-10 to 6-04-11). Patients andMethods: A total of 100 oral biopsies fulfilling the inclusion criteria were collected. The expressionof P53 was observed in biopsies of squamous papilloma and squamous cell carcinoma. Datawas entered and analyzed on SPSS version 20 and was analyzed in same package. Sensitivity,specificity, positive predictive and negative predictive values were calculated along theirconfidence intervals at 95% level. Results: One hundred oral lesions were studied, of which 90cases were of squamous cell carcinoma and 10 cases were of squamous papilloma. Majorityof the patients were male (60%). Mean age was 46 years. P53 IHC stain had sensitivity of 92%and specificity of 80% and diagnostic utility of 91% in lesions of squamous cell carcinoma.Conclusion: P53 is positively expressed in oral squamous cell carcinoma and is negativein squamous papilloma. Hence evaluation of p53 expression can be a useful adjunct in thediagnosis of squamous cell carcinoma, especially in cases where it is difficult to distinguishbetween these two entities on morphological grounds.

Predictive value of p53 expression in the risk of malignant gastrointestinal stromal tumors: Evidence from 19 studies

The current published data on p53 expression and its predictive value in the risk of malignant gastrointestinal stromal tumors (GIST) has are inconclusive. To derive a more precise estimation of the correlation between p53 and the biological behavior of GIST, a meta-analysis was performed. Studies were identified by searching PubMed and Embase. Inclusion criteria were GIST patients, and the evaluation of p53 expression and risk of malignancy. The odds ratio (OR) for a positive rate of p53 in the benign group vs. that in the malignant group and the ORs for the positive rate of p53 in the National Institutes of Health (NIH) very low risk + low risk group (VL+L) vs. the NIH intermediate risk + high risk (I+H) group were calculated with a 95% confidence interval (CI) for each study as an estimation of the predictive value of p53. A total of 19 studies including 1163 patients were involved in this meta-analysis. The overall OR for the positive rate of p53 in the malignant group vs. the benign group revealed that significantly elevated risks of positive p53 in the malignant group were achieved (OR 0.14, 95% CI: 0.06-0.31, P<0.00001, P(heterogeneity)=0.86). Moreover, significantly elevated risks of correlation between p53 expression and the NIH I+H group were achieved in the comparison of the NIH VL+L group vs. the NIH I+H group (OR, 0.25; 95% CI, 0.17-0.38; P<0.00001, P(heterogeneity)=0.04). The results indicate that p53 expression correlates with poor prognosis in GIST and has a close relationship within the NIH I+H group.

Preventive effect of chemical peeling on ultraviolet induced skin tumor formation

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells.

Effect of chemical peeling on photocarcinogenesis

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photo-aged skin. We assessed the photo-chemopreventive effect of several clinically used chemical peeling agents on the ultraviolet-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, and 10% or 35% trichloroacetic acid in distilled water at the right back of ultraviolet-irradiated hairless mice every 2 weeks for glycolic acid, salicylic acid and 10% trichloroacetic acid, and every 4 weeks for 35% trichloroacetic acid for a total of 18 weeks after the establishment of photo-aged mice by irradiation with ultraviolet B range light three times a week for 14 weeks at a total dose of 6.66 J/cm(2) . Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of p53 expression and mRNA expression of cyclooxygenase-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also in the non-treated area. Peeling suppressed retention of p53-positive abnormal cells and reduced mRNA expression of cyclooxygenase-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid and trichloroacetic acid could serve tumor prevention by removing photo-damaged cells.

Identification and phylogenetic comparison of p53 in two distinct mussel species ( Mytilus)

The extent to which humans and wildlife are exposed to anthropogenic challenges is an important focus of environmental research. Potential use of p53 gene family marker(s) for aquatic environmental effects monitoring is the long-term goal of this research. The p53 gene is a tumor suppressor gene that is fundamental in cell cycle control and apoptosis. It is mutated or differentially expressed in about 50% of all human cancers and p53 family members are differentially expressed in leukemic clams. Here, we report the identification and characterization of the p53 gene in two species of Mytilus, Mytilus edulis and Mytilus trossulus, using RT-PCR with degenerate and specific primers to conserved regions of the gene. The Mytilus p53 proteins are 99.8% identical and closely related to clam ( Mya) p53. In particular, the 3′ untranslated regions were examined to gain understanding of potential post-transcriptional regulatory pathways of p53 expression. We found nuclear and cytoplasmic polyadenylation elements, adenylate/uridylate-rich elements, and a K-box motif previously identified in other, unrelated genes. We also identified a new motif in the p53 3′UTR which is highly conserved across vertebrate and invertebrate species. Differences between the p53 genes of the two Mytilus species may be part of genetic determinants underlying variation in leukemia prevalence and/or development, but this requires further investigation. In conclusion, the conserved regions in these p53 paralogues may represent potential control points in gene expression. This information provides a critical first step in the evaluation of p53 expression as a potential marker for environmental assessment.

Oncolysis of human gastric cancers by an E1B 55 kDa-deleted YKL-1 adenovirus

Advanced gastric cancer cannot be treated with surgery or conventional cancer therapy, which has prompted a search for new therapeutic modalities. Previously, we and other groups showed that E1B 55 kDa-deleted recombinant adenoviruses, such as YKL-1, effectively replicate and induce cytotoxicity in p53-deficient cancer cells while sparing normal cells. Here, we investigated selective YKL-1 replication and resultant cytolysis in human gastric cancer cells. The cytopathic effects were obvious in all five gastric cancer cell lines we examined. Evaluation of p53 expression indicated that only the AGS cell line retained functionally normal p53. Nevertheless, AGS was 10-fold more sensitive to YKL-1 than the other cell lines. Transmission electron microscopy showed typical morphological alterations along with efficient replication of YKL-1 in AGS cells. Therefore, YKL-1 induces preferential cytotoxic effects in human gastric cancer cells in a p53-independent manner, making YKL-1 a promising therapeutic agent for human gastric cancers.