uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Differential Expression of Apoptosis, Cell Cycle Regulation and Intermediate Filament Genes in Oral Squamous Cell Carcinomas Associated with Toombak Use in Sudan
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
Show others and affiliations
2011 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 31, no 10, 3345-3351 p.Article in journal (Refereed) Published
Abstract [en]

Previously we used microarray genomic hybridization technology to explore genome-wide profiles of chromosomal aberrations in samples of oral squamous cell carcinomas (OSCCs) and paired normal controls. Based on these findings, 9 genes related to apoptosis, cell cycle regulation and intermediate filament proteins were selected and their differential expression status was examined by real-time quantitative RT-PCR in 26 samples of Sudanese OSCCs and their matched normal controls. The findings were correlated with the habit of toombak use. The mRNA levels of Bcl2, keratin 1, keratin 13 and p53 were significantly lower and the level of survivin was significantly higher in the OSCC samples of the toombak users compared to their paired control samples. A significant down-regulation in keratin I and keratin 13 expression levels was found in the OSCC samples of the non-toombak users compared to their normal control samples. The differential expression of genes related to apoptosis, cell cycle regulation and types I and II keratin could be useful diagnostic markers and provide valuable information for the understanding of oral malignancy in relation to toombak use.

Place, publisher, year, edition, pages
2011. Vol. 31, no 10, 3345-3351 p.
Keyword [en]
Oral squamous cell carcinomas, toombak, genes, apoptosis, cell cycle regulation, intermediate filament proteins, Sudan
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-160724ISI: 000295667700030PubMedID: 21965745OAI: oai:DiVA.org:uu-160724DiVA: diva2:453127
Available from: 2011-11-01 Created: 2011-10-31 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Oral cancer with special reference to virus detection and quantitative gene expression
Open this publication in new window or tab >>Oral cancer with special reference to virus detection and quantitative gene expression
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background. Head and neck cancers (HNC) are among the most common malignancies worldwide, and about 90–92% of oral neoplasias are oral squamous cell carcinomas (OSCC). Alcohol and tobacco consumption have been recognized as the main risk factors for OSCC development. Oncogenic viruses, such as human papillomavirus (HPV) or Epstein-Barr virus (EBV), as well as genetic alterations may also contribute to tumour formation. 

Aims. To study the prevalence of HPV, EBV, Herpes simplex type-1 (HSV-1), and HPV-16 and their integration status as well as the molecular mechanisms that can serve as a basis for the development of OSCC.

Results. In Paper I we reported a statistically significant increase in the prevalence of HPV-16 in oral epithelial dysplasia (OED) and OSCC samples compared to controls. A statistically significant increase was also seen in integrated HPV-16 compared to episomal viral forms when comparing OED and OSCC samples. Paper II reported the detection of HSV-1 in 54% of healthy samples, in 36% of oral leukoplakia samples, and 52% of OSCC samples. However, these differences were not statistically significant. In Paper III we reported a statistically significant increase in the detection of HPV-positive samples when comparing nested polymerase chain reaction (PCR) with single-PCR results in OSCC and fresh oral mucosa. Paper IV reported that the highest prevalence of HPV (65%) was seen in Sudan, while an HSV-1 prevalence of 55% and an EBV prevalence of 80% were seen in the UK. Finally, Paper V reported that the mRNA levels of Bcl-2, keratin 1, keratin 13, and p53 were significantly lower and that the level of survivin was significantly higher in the OSCC samples of the toombak users than in their paired control samples. Significant downregulation in keratin 1 and keratin 13 expression levels was found in the OSCC samples of the non-toombak users relative to their normal control samples.

Conclusion. HPV-16 integration was increased in oral epithelial dysplasia and OSCC compared to normal oral mucosa. Nested PCR is a more accurate method of establishing HPV prevalence in samples containing low copy numbers of HPV DNA. HPV and EBV may be a risk factor in OSCC development. Our findings confirmed the role of survivin in OSCC carcinogenesis and survivin might be interesting as a biomarker to be monitored. The results presented here provide both clinical and biological insights that will bring us closer to the goal of managing this disease and improving treatment and outcomes for future patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1179
Keyword
HPV, EBV, HSV-1, Oral Squamous Cell Carcinoma, Leukoplakia, apopto-sis, cell cycle regulation, intermediate filament proteins.
National Category
Natural Sciences Medical and Health Sciences
Research subject
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-275516 (URN)978-91-554-9476-6 (ISBN)
Public defence
2016-03-18, Skoog-salen, Akademiska sjukhuset, Ingång 79, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2016-02-26 Created: 2016-02-04 Last updated: 2016-03-09

Open Access in DiVA

No full text

Other links

PubMedhttp://ar.iiarjournals.org/content/31/10/3345.full.pdf+html

Authority records BETA

Jalouli, Miranda M.Sand, LarsHirsch, Jan-M.

Search in DiVA

By author/editor
Jalouli, Miranda M.Sand, LarsHirsch, Jan-M.
By organisation
Oral and Maxillofacial Surgery
In the same journal
Anticancer Research
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

pubmed
urn-nbn

Altmetric score

pubmed
urn-nbn
Total: 440 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf