p53 – Page 2 – Oral Cancer News

Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer

Source: 7thspace.com Author: staff P16 and p53 protein expression, and high-risk human papillomavirus (HPV-HR) types have been associated with survival in head and neck cancer (HNC). Evidence suggests that multiple molecular pathways need to be targeted to improve the poor prognosis of HNC. Purpose: This study examined the individual and joint effects of tumor markers for differences in predicting HNC survival. P16 and p53 expression were detected from formalin-fixed, paraffin-embedded tissues by immunohistochemical staining. HPV DNA was detected by PCR and DNA sequencing in 237 histologically confirmed HNC patients. Results: Overexpression of p16 (p16+) and p53 (p53+) occurred in 38% and 48% of HNC tumors, respectively. HPV-HR was detected in 28% of tumors. Worse prognosis was found in tumors that were p53+ (disease-specific mortality: adjusted hazard ratios, HR=1.9, 95% CI: 1.04-3.4) or HPV (overall survival: adj. HR=2.1, 1.1-4.3) but no association in survival was found by p16 status. Compared to the molecular marker group with the best prognosis (p16+/p53/HPV-HR: referent), the p16/p53+/HPV group had the lowest overall survival (84% vs. 60%, p<0.01; HR=4.1, 1.7-9.9) and disease-specific survival (86% vs. 66%, p<0.01; HR=4.0, 1.5-10.7). Compared to the referent, the HRs of the other six joint biomarker groups ranged from 1.6-3.4 for overall mortality and 0.9-3.9 for disease-specific mortality. Conclusion: The p16/p53/HPV joint groups showed greater distinction in clinical outcomes compared to results based on the individual biomarkers alone. This finding suggests that assessing multiple molecular markers in HNC patients will better predict the diverse outcomes and potentially the type of treatment [...]

Oral Cancer Foundation News Team - A2010-02-13T10:22:17-07:00February, 2010|Oral Cancer News|

Comparative prognostic value of HPV16 E6 mRNA compared with in situ hybridization for human oropharyngeal squamous carcinoma

Source: Journal of Clinical Oncology, 10.1200/JCO.2009.23.1670 Author: Wei Shi et al. Purpose: A significant proportion of oropharyngeal squamous cell carcinomas (OSCC) are associated with the human papilloma virus (HPV), particularly HPV16. The optimal method for HPV determination on archival materials however, remains unclear. We compared a quantitative real-time polymerase chain reaction (qRT-PCR) assay for HPV16 mRNA to a DNA in situ hybridization (ISH) method, and evaluated their significance for overall (OS) and disease-free (DFS) survival. Patients and Methods: Matched, archival biopsies from 111 patients with OSCC were evaluated for HPV16 using a qRT-PCR for E6 mRNA and ISH for DNA. Immunohistochemistry for p16, p53, and epidermal growth factor receptor were also performed. Results: HPV16 E6 mRNA was positive in 73 (66%) of 111 samples; ISH was positive in 62 of 106 samples (58%), with 86% concordance. P16 was overexpressed in 72 samples (65%), which was strongly associated with HPV16 status by either method. E6 mRNA presence or p16 overexpression were significantly associated with superior OS; E6 mRNA, HPV16 ISH, or p16 were all significantly associated with DFS. On multivariate analysis adjusted for age, stage, and treatment, positive E6 mRNA was the only independent predictor for superior OS; for DFS, p16 expression or HPV16 status determined by either method was significant. Conclusion: The prevalence of HPV16 in OSCC ranges from 58% to 66%, in a recently treated Canadian cohort. Classification of HPV-positivity by HPV16 E6 mRNA, HPV16 ISH or p16 immunohistochemistry (IHC) is associated with improved DFS. However, the latter two [...]

Oral Cancer Foundation News Team - A2009-11-05T07:30:00-07:00November, 2009|Oral Cancer News|

Researchers pinpoint a new enemy for tumor-suppressor P53

Source: biocompare.com Author: staff Researchers at The University of Texas M. D. Anderson Cancer Center have identified a protein that marks the tumor suppressor p53 for destruction, providing a potential new avenue for restoring p53 in cancer cells. The new protein, called Trim24, feeds p53 to a protein-shredding complex known as the proteasome by attaching targeting molecules called ubiquitins to the tumor suppressor, the team reported this week in the Proceedings of the National Academy of Sciences Online Early Edition. "Targeting Trim24 may offer a therapeutic approach to restoring p53 and killing tumor cells," said senior author Michelle Barton, Ph.D., professor in M. D. Anderson's Department of Biochemistry and Molecular Biology. The discovery is based on an unusual approach to studying p53, which normally forces potentially cancerous cells to kill themselves and is shut down or depleted in most human cancers. Studies of the p53 protein and gene tend to focus on cancer cell lines or tumors, where the dysfunction already is established, Barton said. "We wanted to purify p53 from normal cells to better understand the mechanisms that regulate it." The team developed a strain of mice with a biochemical tag attached to every p53 protein expressed. After first assuring that the tagged p53 behaved like normal p53, the team then used the tag, or hook, to extract the protein. "We could then identify proteins that were attached to p53, interacting with it, through mass spectrometry," Barton said. They found Trim24, a protein previously unassociated with p53 that is [...]

Oral Cancer Foundation News Team - A2009-06-30T16:06:34-07:00June, 2009|Oral Cancer News|

A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

Source: 7thspace.com Author: Paola Galli et al. The purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population. Methods: Two hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms. Results: We found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08-4.56), and a protective effect for those carrying the p53 exon 4- p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47-0.92). From the gene-environment interaction analysis we found that individuals aged <45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10-78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23-1.16). Conclusion: Our study provides for [...]

Oral Cancer Foundation News Team - A2009-05-09T09:35:04-07:00May, 2009|Oral Cancer News|

How eating fruit and vegetables can improve cancer patients’ response to chemotherapy

Source: www.biocompare.com Author: staff UC Riverside study describes how naturally occurring apigenin facilitates the death of cancer cells The leading cause of death in all cancer patients continues to be the resistance of tumor cells to chemotherapy, a form of treatment in which chemicals are used to kill cells. Now a study by UC Riverside biochemists that focuses on cancer cells reports that ingesting apigenin – a naturally occurring dietary agent found in vegetables and fruit – improves cancer cells' response to chemotherapy. Xuan Liu, a professor of biochemistry, and Xin Cai, a postdoctoral researcher working in her lab, found that apigenin localizes tumor suppressor p53, a protein, in the cell nucleus – a necessary step for killing the cell that results in some tumor cells responding to chemotherapy. The study, published this week in the online early edition of the Proceedings of the National Academy of Sciences, provides a novel approach to conquer tumor resistance to chemotherapy, and suggests an avenue for developing safe chemotherapy via naturally occurring agents. Normally, cells have low levels of p53 diffused in their cytoplasm and nucleus. When DNA in the nucleus is damaged, p53 moves to the nucleus where it activates genes that stop cell growth and cause cell death. In this way, p53 ensures that cells with damaged DNA are killed. In many cancers, p53 is rendered inactive by a process called cytoplasmic sequestration. Apigenin is able to activate p53 and transport it into the nucleus, resulting in a stop to cell [...]

Oral Cancer Foundation News Team - A2008-10-29T05:51:00-07:00October, 2008|Oral Cancer News|

Tumour therapy drug to be reviewed

Source: PharmacyEurope (www.pharmacyeurope.net) Author: staff The European Medicines Agency (EMEA) is to review a drug targeted at the treatment of recurrent cancer of the head and neck. Advexin is designed to restore the tumour suppressing gene p53 that is blocked in the majority of tumours. If approved, it will be the first gene therapy product approved for use in Europe. "This acceptance of the Advexin Marketing Authorisation Application (MAA) by the EMEA marks an historic point in the growth of personalised medicine, and the treatment of head and neck cancer," said Max Talbott, senior vice president of worldwide commercial development at the drug's developer, Introgen Therapeutics. "This action by the EMEA underscores the rapidly increasing importance of biomarkers, in the development and regulatory approval processes for targeted therapeutics. We look forward to working with the EMEA during the Advexin review process, which we hope will lead to the first gene therapy product in Europe." The MAA follows a phase III study of Advexin in patients with recurrent, refractory squamous cell carcinoma of the head and neck. It successfully achieved its goal, which was survival or tumour response in patients

Oral Cancer Foundation News Team - A2008-08-19T05:39:23-07:00August, 2008|Oral Cancer News|