Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9

P53 Related Abstracts

9 Molecular Study of P53- and Rb-Tumor Suppressor Genes in Human Papilloma Virus-Infected Breast Cancers

Authors: Shakir H. Mohammed Al-Alwany, Saad Hasan M. Ali, Ibrahim Mohammed S. Shnawa

Abstract:

The study was aimed to define the percentage of detection of high-oncogenic risk types of HPV and their genotyping in archival tissue specimens that ranged from apparently healthy tissue to invasive breast cancer by using one of the recent versions of In Situ Hybridization(ISH) 0.2. To find out rational significance of such genotypes as well as over expressed products of mutants P53 and RB genes on the severity of underlying breast cancers. The DNA of HPV was detected in 46.5 % of tissues from breast cancers while HPV DNA in the tissues from benign breast tumours was detected in 12.5%. No HPV positive–ISH reaction was detected in healthy breast tissues of the control group. HPV DNA of genotypes (16, 18, 31 and 33) was detected in malignant group in frequency of 25.6%, 27.1%, 30.2% and 12.4%, respectively. Over expression of p53 was detected by IHC in 51.2% breast cancer cases and in 50% benign breast tumour group, while none of control group showed P53- over expression. Retinoblastoma protein was detected by IHC test in 49.7% of malignant breast tumours, 54.2% of benign breast tumours but no signal was reported in the tissues of control group. The significance prevalence of expression of mutated p53 & Rb genes as well as detection of high-oncogenic HPV genotypes in patients with breast cancer supports the hypothesis of an etiologic role for the virus in breast cancer development.

Keywords: Breast Cancer, human papilloma virus, P53

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8 Anti-Cancerous Activity of Sargassum siliquastrum in Cervical Cancer: Choreographing the Fly's Danse Macabre

Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

Abstract:

Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: Cervical Cancer, P53, sargassum siliquastrum, antiproleferation

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7 Role of Molecular Changes and Immunohistochamical in Early Detection of Colon Cancer

Authors: Fatimah Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of colon cancer in Saudi patients. Our results were carried out on 48 patients colon cancer. We obtained our data from laboratory in King Khalid university hospital. The specimens were taken (48) patients with colon cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as I in tow patients (male and female) and grade 2 in 42 patients (29 male and 13 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining , immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients of adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscularis layer. With advancing the disease, there were haemorge in blood and increase in lymphocytes and increase number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20,PCNA,P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for pcan and the grades. In our sections, there were strong reactions in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of colon cancer.

Keywords: Colon Cancer, P53, DNA-CK20, PCNA

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6 Study of Relation between P53 and Mir-146a Rs2910164 Polymorphism in Cervical Lesion

Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: Cervical Cancer, Polymorphism, P53, miR-146a, rs2910164

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5 Investigation of Possible Precancerous Viral Markers in Dental Follicles of Asymptomatic Impacted Teeth

Authors: Serap Keskin Tunç, Cennet Neslihan Eroğlu, Sevinç Şahin, Selda Seçkin

Abstract:

It has been suggested that various viruses may play a role in the pathogenesis of cancerous oral lesions in the literature. The aim of this study was to investigate the presence of both possible precancerous viral markers (HPV, HHV8, HSV1, HSV2, and EBV), and p53 and Ki-67 in the dental follicles of asymptomatic impacted teeth. A hundred healthy volunteers, older than 18 years old, included in the study. Dental follicles of extracted impacted teeth were excised and fixated in 10% formaldehyde. Histopathological and immunohistochemical examinations using HPV (containing HPV 8 and HPV 11), p16 (containing HPV 16), HHV8, HSV1, HSV2, EBV, p53 and Ki-67 antibodies were carried out. Also, the immunohistochemical results were correlated with the clinicopathological feature by Chi-square test statistically No dysplasia or neoplasm was observed. 62% of the cases were positive for p16, 32% were positive for EBV, 26% were positive for HSV1, immunohistochemically. All cases were immunonegative for HPV, HSV2, and HHV8. There was statistically significant correlation between overexpression of p53 with both EBV and p16 positivity (p<0.05). Direct correlation between higher expression of Ki-67 between EBV immunopositivity was detected (p<0.05). Thus, these viruses may be suggested to show trophism to the dental follicles acting as a reservoir. In conclusion, all dental follicles of extracted impacted teeth should be examined histopathologically in order to detect and prevent possible viral oncogenesis.

Keywords: P53, Ki67, dental follicles, precancerous markers viral markers

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4 Spatio-Temporal Properties of p53 States Raised by Glucose

Authors: Md. Jahoor Alam

Abstract:

Recent studies suggest that Glucose controls several lifesaving pathways. Glucose molecule is reported to be responsible for the production of ROS (reactive oxygen species). In the present work, a p53-MDM2-Glucose model is developed in order to study spatiotemporal properties of the p53 pathway. The systematic model is mathematically described. The model is numerically simulated using high computational facility. It is observed that the variation in glucose concentration level triggers the system at different states, namely, oscillation death (stabilized), sustain and damped oscillations which correspond to various cellular states. The transition of these states induced by glucose is phase transition-like behaviour. Further, the amplitude of p53 dynamics with the variation of glucose concentration level follows power law behaviour, As(k) ~ kϒ, where, ϒ is a constant. Further Stochastic approach is needed for understanding of realistic behaviour of the model. The present model predicts the variation of p53 states under the influence of glucose molecule which is also supported by experimental facts reported by various research articles.

Keywords: Glucose, P53, oscillation, temporal behavior

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3 Role of Molecular Changes and Immunohistochemical in Early Detection of Liver Cancer

Authors: Fatimah A. Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: Cancer, Liver, Dna, Molecular Changes, P53, PCNA, CK20, cytometry analysis, immunohistochemical

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2 Glioblastoma: Prognostic Value of Clinical, Histopathological and Immunohistochemical (p53, EGFR, VEGF, MDM2, Ki67) Parameters

Authors: Sujata Chaturvedi, Ishita Pant, Deepak Kumar Jha, Vinod Kumar Singh Gautam, Chandra Bhushan Tripathi

Abstract:

Objective: To describe clinical, histopathological and immunohistochemical profile of glioblastoma in patients and to correlate these findings with patient survival. Material and methods: 30 cases of histopathologically diagnosed glioblastomas were included in this study. These cases were analysed in detail for certain clinical and histopathological parameters. Immunohistochemical staining for p53, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mouse double minute 2 homolog (MDM2) and Ki67 was done and scores were calculated. Results of these findings were correlated with patient survival. Results: A retrospective analysis of the histopathology records and clinical case files was done in 30 cases of glioblastoma (WHO grade IV). The mean age of presentation was 50.6 years with a male predilection. The most common involved site was the frontal lobe. Amongst the clinical parameters, age of the patient and extent of surgical resection showed a significant correlation with the patient survival. Histopathological parameters showed no significant correlation with the patient survival, while amongst the immunohistochemical parameters expression of MDM2 showed a significant correlation with the patient survival. Conclusion: In this study incorporating clinical, histopathological and basic panel of immunohistochemistry, age of the patient, extent of the surgical resection and expression of MDM2 showed significant correlation with the patient survival.

Keywords: P53, VEGF, Ki67, glioblastoma, EGFR, MDM2

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1 The Transcriptional Regulation of Human LRWD1 through DNA Methylation

Authors: Yen-Ni Teng, Hsing-Yi Chen, Hsien-An Pan, Yung-Ming Lin, Hany A. Omar, Jui-Hsiang Hung

Abstract:

Leucine-rich repeats and WD repeat domain containing 1 (LRWD1) is highly expressed in the testes of healthy males. On the other hand, LRWD1 is significantly down-regulated in the testicular tissues of patients with severe spermatogenic defects. In our study, the downregulation of LRWD1 expression by shRNA caused a significant reduction of cell growth and mitosis and a noteworthy increase in the cell microtubule atrophy rate. Here, we used EMBOSS CpG plot analysis to explore the promoter region of LRWD1 gene. We found that CpG islands are located between positions -253 to +5 nucleotides upstream from the LRWD1 transcription start site. Luciferase reporter assay revealed that the hypermethylation of the LRWD1 promoter reduced the transcription activity in cells. In addition, quantitative methylation-specific PCR and immunostaining showed that the methylation inhibitor, 5-Aza-2'-deoxycytidine, increased LRWD1 promoter activity, LRWD1 mRNA, protein expression and cell viability. Whereas, the methylation activator, S-adenosylmethionine, caused opposite effects. The overexpression of p53 and Nrf2 in NT2/D1 cells increased LRWD1 promoter activity while 5-fluorodeoxyuridine decreased it. In conclusion, this study highlights evidence that the methylation status of LRWD1 promoter is associated with LRWD1 expression. Since the expression level of LRWD1 plays an important role in spermatogenesis, the methylation status of LRWD1 may serve as a novel molecular diagnostic or therapeutic approach in male's infertility.

Keywords: DNA Methylation, P53, NrF2, LRWD1

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