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Farnebo, Lovisa
Publications (10 of 12) Show all publications
Kiug, T. E., Hentze, M., Schytte, S., Farnebo, L., Rikardsen, O., Sihvo, E., . . . Makitie, A. (2019). Laryngo-tracheal resections in the Nordic countries: an option for further centralization?. European Archives of Oto-Rhino-Laryngology, 276(5), 1545-1548
Open this publication in new window or tab >>Laryngo-tracheal resections in the Nordic countries: an option for further centralization?
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2019 (English)In: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 276, no 5, p. 1545-1548Article in journal (Refereed) Published
Abstract [en]

Purpose

We aimed to obtain information on the number of Nordic centers performing tracheal resections, crico-tracheal resections, and laryngo-tracheal reconstructions, as well as the patient volume and the standard regimens associated with these procedures.

Methods

Consultants at all Departments of Otorhinolaryngology—Head and Neck Surgery (ORL-HNS, n = 22) and Thoracic Surgery (n = 21) in the five Nordic countries were invited (April 2018—January 2019) to participate in an online survey.

Results

All 43 departments responded to the survey. Twenty departments declared to perform one or more of the three types of tracheal resections. At five hospitals, departments of ORL-HNS and Thoracic Surgery perform these operations in collaboration. Hence, one or more of the tracheal operations in question are carried out at 15 centers. The median annual number of tracheal operations per center is five (range 1–20). Great variations were found regarding contraindications (relative and absolute) for surgery, the use of guardian sterno-mental sutures (all patients, 33%; selected cases, 40% of centers), prophylactic antibiotic therapy (cefuroxime +/− metronidazole, penicillin +/− metronidazole, clindamycin, imipenem, or none), post-operative follow-up time (range: children: 3–120 months; adults: 0–60 months), and the performance of post-operative bronchoscopy.

Conclusions

Fifteen centers each perform a low number of annual operations with significant variations in the selection of patients and the clinical setup, which raises the question if a higher degree of collaboration and centralization would be warranted. We encourage Nordic transnational collaboration, pursuing alignment on central management issues, and establishment of a common prospective database for future tracheal resection surgery.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Tracheal resection; Crico-tracheal resection; Management; Nordic countries
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-156918 (URN)10.1007/s00405-019-05384-x (DOI)000464861500037 ()30888495 (PubMedID)2-s2.0-85063093618 (Scopus ID)
Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-06-03Bibliographically approved
Melissaridou, S., Wiechec, E., Magan, M., Jain, M. V., Chung, M. K., Farnebo, L. & Roberg, K. (2019). The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer.. Cancer Cell International, 19(16)
Open this publication in new window or tab >>The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer.
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2019 (English)In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 19, no 16Article in journal (Refereed) Published
Abstract [en]

Background

Head and Neck Squamous Cell Carcinoma (HNSCC) tumors are often resistant to therapies. Therefore searching for predictive markers and new targets for treatment in clinically relevant in vitro tumor models is essential. Five HNSCC-derived cell lines were used to assess the effect of 3D culturing compared to 2D monolayers in terms of cell proliferation, response to anti-cancer therapy as well as expression of EMT and CSC genes.

Methods

The viability and proliferation capacity of HNSCC cells as well as induction of apoptosis in tumor spheroids cells after treatment was assessed by MTT assay, crystal violet- and TUNEL assay respectively. Expression of EMT and CSC markers was analyzed on mRNA (RT-qPCR) and protein (Western blot) level.

Results

We showed that HNSCC cells from different tumors formed spheroids that differed in size and density in regard to EMT-associated protein expression and culturing time. In all spheroids, an up regulation of CDH1, NANOG and SOX2 was observed in comparison to 2D but changes in the expression of EGFR and EMT markers varied among the cell lines. Moreover, most HNSCC cells grown in 3D showed decreased sensitivity to cisplatin and cetuximab (anti-EGFR) treatment.

Conclusions

Taken together, our study points at notable differences between these two cellular systems in terms of EMT-associated gene expression profile and drug response. As the 3D cell cultures imitate the in vivo behaviour of neoplastic cells within the tumor, our study suggest that 3D culture model is superior to 2D monolayers in the search for new therapeutic targets.

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Cancer stem cells; Drug response; Epithelial–mesenchymal transition; Head and Neck Squamous Cell Carcinoma; Spheroids
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-153947 (URN)10.1186/s12935-019-0733-1 (DOI)000455593400001 ()30651721 (PubMedID)2-s2.0-85059943217 (Scopus ID)
Note

Funding agencies: Korea-Sweden Joint Research Programme; Swedish Cancer Society [2017/301]; County Council of Ostergotland; Research Funds of Linkoping University Hospital; Cancer Foundation of Ostergotland

Available from: 2019-01-21 Created: 2019-01-21 Last updated: 2019-03-29Bibliographically approved
Farnebo, L., Malila, N., Makitie, A. & Laurell, G. (2016). Early death among head and neck cancer patients. Current Opinion in Otolaryngology & Head and Neck Surgery, 24(2), 115-120
Open this publication in new window or tab >>Early death among head and neck cancer patients
2016 (English)In: Current Opinion in Otolaryngology & Head and Neck Surgery, ISSN 1068-9508, E-ISSN 1531-6998, Vol. 24, no 2, p. 115-120Article, review/survey (Refereed) Published
Abstract [en]

Purpose of reviewManagement of advanced head and neck cancer (HNC) is characterized by high mortality. Furthermore, the treatment involves significant burden to patients and high costs to healthcare systems. Recognizing the risks of early death in patients with a high probability of noncurable disease is important for each individual treatment decision-making. It is thus critical to consider the benefits and side-effects of the planned treatment in relation to the expected survival and to discuss these factors with the patient. However, only few studies have documented early death in HNC patients, that is, during the first posttreatment 6 months. We performed a systematic literature review to find the incidence of this phenomenon and to outline the probable cause.Recent findingsEarly mortality in patients with HNC can be explained either by direct effect of malignant disease, may be related to comorbidities, or secondary to the treatment. These factors act together resulting in expected or unexpected early death.SummaryThe present review provides information on the mechanisms leading to early phase mortality (<6 months) after management of HNC. It also reports the incidence of this phenomenon among Finnish and Swedish patient populations.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2016
Keywords
chemotherapy; mortality; radiotherapy; surgery; survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127042 (URN)10.1097/MOO.0000000000000236 (DOI)000371888600005 ()26735585 (PubMedID)
Note

Funding Agencies|Helsinki University Hospital Funds

Available from: 2016-04-13 Created: 2016-04-13 Last updated: 2017-11-30
Farnebo, L., Stjernstrom, A., Fredrikson, M., Ansell, A., Garvin, S. & Thunell, L. (2015). DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck. DNA Repair, 31, 64-72
Open this publication in new window or tab >>DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck
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2015 (English)In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 31, p. 64-72Article in journal (Refereed) Published
Abstract [en]

Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors with a high rate of early recurrences, second primary tumors, and mortality. Despite advances in diagnosis and treatment over the past decades, the overall 5-year survival rate remains around 50%. Since the head-and neck-region is continuously exposed to potentially DNA-damaging exogenous and endogenous factors, it is reasonable to expect that the DNA repair genes play a part in the development, progression, and outcome of HNSCC. The aim of this study was to investigate the SNPs XPC A499V, XPD K751Q XRCC1 R399Q and XRCC3 T241M as potential risk factors and indicators of survival among Caucasian patients. One-hundred-sixty-nine patients as well as 344 healthy controls were included and genotyped with PCR-RFLP. We showed that XPC A499V was associated with increased risk of HNSCC, especially laryngeal carcinoma. Among women, XPD K751Q was associated with increased risk of oral SCC. Furthermore, XPD homozygous mutant individuals had the shortest survival time, a survival time that increased however after full dose radiotherapy. Wild-type individuals of XRCC3 T241M demonstrated an earlier age of onset. HPV-positive never smokers had lower frequencies of p53 mutation. Among HNSCC patients, HPV-positivity was significantly associated with XRCC1 R399Q homozygous mutant genotype. Moreover, combinations of putative risk alleles seemed to act synergistically, increasing the risk of HNSCC. In conclusion, our results suggest that SNPs of the DNA repair genes XPC, XPD, XRCC1, and XRCC3 may affect risk and survival of HNSCC. (C) 2015 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Head and neck squamous cell carcinoma; XPC; XPD; HPV; p53; Overall survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120212 (URN)10.1016/j.dnarep.2015.05.003 (DOI)000357138600007 ()26001739 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society; Laryngfonden

Available from: 2015-07-21 Created: 2015-07-20 Last updated: 2017-12-04
Garvin, S., Tiefenböck, K., Farnebo, L., Thunell, L., Farnebo, M. & Roberg, K. (2015). Nuclear expression of WRAP53 beta is associated with a positive response to radiotherapy and improved overall survival in patients with head and neck squamous cell carcinoma. Oral Oncology, 51(1), 24-30
Open this publication in new window or tab >>Nuclear expression of WRAP53 beta is associated with a positive response to radiotherapy and improved overall survival in patients with head and neck squamous cell carcinoma
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2015 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 51, no 1, p. 24-30Article in journal (Refereed) Published
Abstract [en]

Objectives: Today there are no reliable predictive markers for radiotherapy response in head and neck squamous cell carcinoma (HNSCC), leading to both under-and over-treatment of patients, personal suffering, and negative socioeconomic effects. Inherited mutation in WRAP53 beta (WD40 encoding RNA Antisense to p53), a protein involved in intracellular trafficking, dramatically increases the risk of developing HNSCC. The purpose of this study was to investigate whether WRAP53 beta can predict response to radiotherapy in patients with HNSCC. Materials and methods: Tumor biopsies from patients with HNSCC classified as responders or non-responders to radiotherapy were examined for the expression of the WRAP53 beta protein and single nucleotide polymorphisms in the corresponding gene employing immunohistochemistry and allelic discrimination, respectively. In addition, the effect of RNAi-mediated downregulation of WRAP53 beta on the intrinsic radiosensitivity of two HNSCC cell lines was assed using crystal violet and clonogenic assays. Results: Nuclear expression of WRAP53 beta was significantly associated with better response to radiotherapy and improved patient survival. Downregulation of WRAP53 beta with siRNA in vitro enhanced cellular resistance to radiation. Conclusions: Our findings suggest that nuclear expression of WRAP53 beta promotes tumor cell death in response to radiotherapy and is a promising predictor of radiotherapy response in patients with HNSCC.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Head and neck cancer; Radiotherapy; Predictive factors; Survivin; WRAP53
National Category
Cancer and Oncology Otorhinolaryngology
Identifiers
urn:nbn:se:liu:diva-113161 (URN)10.1016/j.oraloncology.2014.10.003 (DOI)000346210900007 ()25456005 (PubMedID)
Note

Funding Agencies|Swedish Laryng Foundation; Ake Wiberg Foundation; Swedish Cancer Society [2008/552, 2010/545]; County Council of Ostergotland; Research Funds of Linkoping University Hospital

Available from: 2015-01-14 Created: 2015-01-12 Last updated: 2017-12-05
Farnebo, L., Tiefenböck, K., Ansell, A., Thunell, L., Garvin, S. & Roberg, K. (2013). Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients. International Journal of Cancer, 133(8), 1994-2003
Open this publication in new window or tab >>Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients
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2013 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 8, p. 1994-2003Article in journal (Refereed) Published
Abstract [en]

Head and neck squamous cell carcinoma (HNSCC) is a malignancy that is associated with severe mortality despite advances in therapy. Todays standard treatment most commonly includes radiotherapy, often combined with chemotherapy or surgery. There are so far no established biomarkers to predict response to radiation, and thus the aim of this study was to investigate a series of markers that could potentially identify HNSCC patients who would benefit from radiotherapy. The selected markers, both proteins (epidermal growth factor receptor, survivin and p53), and single nucleotide polymorphisms (SNPs) in the genes of XRCC3, XRCC1, XPC, XPD, MDM2, p53 and FGFR4 were correlated to the response to radiotherapy and overall survival. Investigations were performed on pretreatment tumor biopsies from patients classified as responders or nonresponders to radiotherapy. Protein expression was examined using immunohistochemistry and the genotyping of specific SNPs was analyzed using PCR-RFLP or pyrosequencing. We found that survivin expression was significantly stronger in the responder group (p = 0.003) and that patients with a strong survivin expression had a significantly better overall survival (p andlt; 0.001). Moreover, downregulation of survivin by siRNA in two HNSCC cell lines significantly decreased their sensitivity to radiation. Among the SNPs analyzed, patients with the XPD Lys751Gln SNP had a significantly shorter overall survival (p = 0.048), and patients with the FGFR4 Gly388Arg SNP had a significantly longer overall survival (p = 0.010). In conclusion, our results suggest that survivin plays an important role in the response to radiotherapy and may be a useful marker for predicting radiotherapy response in patients with HNSCC. less thanbrgreater than less thanbrgreater thanWhats new? Resistance to radiation therapy is a significant problem in the treatment of head and neck squamous cell carcinoma (HNSCC) and has created a need for the discovery of markers predictive of radiotherapy response. One promising marker is survivin, an inhibitor of apoptosis. Here, in pre-treatment biopsies from 40 patients with HNSCC, strong survivin expression was significantly associated with response to radiotherapy and increased overall survival. The data also indicate that single nucleotide polymorphisms in the genes XPD and FGFR4 are other possible predictors of overall survival after radiotherapy.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
Keywords
head and neck tumors, radiotherapy, survivin, single nucleotide polymorphism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-97229 (URN)10.1002/ijc.28200 (DOI)000322908600025 ()
Note

Funding Agencies|Swedish Cancer Society|2008/5522010/545|Swedish Laryng Foundation||Foundation of Ake Wiberg||County Council of Ostergotland||Research Funds of Linkoping University Hospital||

Available from: 2013-09-06 Created: 2013-09-05 Last updated: 2017-12-06
Farnebo, L., Jerhammar, F., Ceder, R., Grafström, R. C., Vainikka, L., Thunell, L., . . . Roberg, K. (2011). Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines. Journal of Oral Pathology & Medicine, 40(10), 739-746
Open this publication in new window or tab >>Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines
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2011 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 40, no 10, p. 739-746Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.

METHODS: The expression of epidermal growth factor receptor, survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.

RESULTS: Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (r=0.36, p=0.02). The combination of survivin, Bax, Bcl-2, Bcl-XL, cyclooxygenase-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r=0.553, p<0.001).

CONCLUSION: These data indicate that the intrinsic radiosensitivity of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.

Place, publisher, year, edition, pages
John Wiley and sons, 2011
Keywords
head and neck tumors, radiotherapy, survivin, Bcl-2 family, p53 Arg72Pro
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-61585 (URN)10.1111/j.1600-0714.2011.01036.x (DOI)000296607200002 ()
Note
Funding agencies|Swedish Laryng Foundation||County Council of Ostergotland (OLL)||Swedish Cancer Foundation||Foundation of Olle Engkvist||Linkoping University Hospital||Available from: 2010-11-16 Created: 2010-11-16 Last updated: 2017-12-12Bibliographically approved
Farnebo, L. (2010). Predictive markers: for treatment sensitivity in head and neck squamous cell carcinoma. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Predictive markers: for treatment sensitivity in head and neck squamous cell carcinoma
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Head and neck cancer is the sixth most common cancer world wide. In Sweden approximately 850 new cases are diagnosed each year, and two thirds are men. The past decades of improved treatment strategies have unfortunately not significantly improved the five-year survival rates for this group of patients. Therefore, it is important to rapidly find combinations of new and strong predictive markers for treatment response. Different predictive markers have been investigated for decades, without succeeding in finding means to securely predict response to treatment. Models to combine markers are called for.

The aim of this thesis was to test multiple predictive markers on both gene and protein level to evaluate their predictive value for radiotherapy and cisplatin response. Furthermore, to combine, and correlate them to treatment response in order to extract the panel of markers that strongest correlated to the investigated treatment. Cell lines derived from 42 patients with head and neck squamous cell carcinoma (HNSCC) were used for protein quantification with Western blot and ELISA of the proteins survivin, Epidermal Growth Factor Receptor, Bcl-2, Bcl-XL, Bax, Bad, Bak, PUMA, Heat shock protein 70, MDM2, p53, SMAD4, Cyclooxygenase-2, and Cyclin D1. The expression of the selected proteins was related to the mean expression of normal oral keratinocytes (NOK) from healthy individuals. Furthermore, mutations in the p53 gene, along with single nucleotide polymorphisms in the genes of p53, MDM2, FGFR4, XRCC1, XRCC3, XPD, and XPC were analysed. To allow a large number of predictive markers on both protein and gene level to be combined and correlated to treatment response, the number of negative points (NNP) model was introduced. Both correlations of sensitivity to radiotherapy and to cisplatin treatment was analysed among the cell lines. In the first paper, including nine cell lines, the panel of EGFR, survivin, and splice site/missense p53 mutations correlated strongest to radioresponse. In paper II, 42 cell lines were used and the combination of survivin, Bcl-2, Bcl-XL, Bax, COX-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse. In paper IV, the panel correlating strongest with cisplatin sensitivity consisted of EGFR, Hsp70, Bax, and Bcl-2 in combination with SNPs in the DNA-repair genes XRCC3 and XPD.

The predisposition of the FGFR4 Gly388Arg polymorphism for the development of HNSCC was investigated in paper III. DNA was isolated from 110 tumour biopsies, and restriction fragment length polymorphism analysis showed that 58% of the individuals in the control group carried the FGFR4 Arg388 allele, whereas the frequency in the tumour group was 45%. The Gly388 allele gave a significantly higher risk of developing HNSCC, suggesting Gly388 to be the risk allele for cancer development. Furthermore, a novel mutation was found in the FGFR4 gene. The influence of this new mutation is however unknown.

In conclusion, predictive markers for treatment sensitivity need to be combined to receive an accurate prediction of treatment response.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. p. 84
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1205
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-61586 (URN)978-91-7393-319-3 (ISBN)
Public defence
2010-11-12, Elsa Brändströmsalen, Campus US, Linköpings universitet, Linköping, 09:00
Opponent
Supervisors
Available from: 2010-11-16 Created: 2010-11-16 Last updated: 2012-05-09Bibliographically approved
Ansell, A., Farnebo, L., Grénman, R., Roberg, K. & Thunell, L. (2009). Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer. Oral Oncology, 45(1), 23-29
Open this publication in new window or tab >>Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer
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2009 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 45, no 1, p. 23-29Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate the predisposition of the FGFR4 Gly/Arg polymorphism for development of head and neck squamous cell carcinoma (HNSCC) and, furthermore, to examine if the FGFR4 Arg(388) allele can be associated with resistance to chemo-and radiotherapy.

When analysing 110 tumour biopsies a significant 1.7-fold increased risk to develop HNSCC in individuals carrying the Gly(388) allele (p = 0.026) was found. Moreover a 2-fold increased risk for mates harbouring the Gly(388) allele (p = 0.031) to develop HNSCC was detected. In 39 HNSCC cell lines the role of the Arg(388) allele for radiation and cisplatin sensitivity was investigated. Our results show no rote of the Arg(388) allele for the radiosensitivity (p = 0.996) but indicate a tendency to increased cisplatin sensitivity (p = 0.141). When screening the transmembrane and kinase domains in the FGFR4 gene a novel mutation, probably generating a truncated protein lacking exons 14-18, was found in six of eight selected cell lines.

Taken together, we have here identified a marker that predicts the risk to develop HNSCC and possibly the sensitivity to cisplatin as well as a novel. mutation in the FGFR4 gene.

Place, publisher, year, edition, pages
Elsevier, 2009
Keywords
Oral tumours, Radiotherapy, Chemotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-16724 (URN)10.1016/j.oraloncology.2008.03.007 (DOI)000262607900005 ()18487077 (PubMedID)
Available from: 2009-02-14 Created: 2009-02-13 Last updated: 2017-12-14Bibliographically approved
Farnebo, L., Jedlinski, A., Ansell, A., Vainikka, L., Thunell, L., Grenman, R., . . . Roberg, K. (2009). Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines. International Journal of Molecular Medicine, 24(4), 549-556
Open this publication in new window or tab >>Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines
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2009 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 24, no 4, p. 549-556Article in journal (Refereed) Published
Abstract [en]

The present study was undertaken to evaluate the possibility of using a panel of proteins and single nucleotide polymorphisms (SNPs) involved in apoptosis, growth control, and DNA repair as predictive markers for cisplatin sensitivity. For this purpose the intrinsic cisplatin sensitivity (ICS) was determined in 39 cell lines derived from squamous cell carcinomas of the head and neck using a colony-forming assay. In these cell lines and in normal oral keratinocytes (NOK), the expression of epidermal growth factor receptor (EGFR), Hsp70, Bax, Bcl-2, Bcl-XL, survivin, and COX-2 was determined. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearsons correlation test showed that EGFR was the only protein that was significantly correlated to the ICS (r=0.388, p=0.015). The combination of EGFR, Hsp70, Bax, and Bcl-2 gave the strongest correlation (r=0.566, p andlt;= 0.001), whereas Bax alone had the second highest influence on the ICS. Furthermore, all four SNPs within genes involved in DNA repair, i.e. XPC, XPD, XRCC1, and XRCC3, tended to influence the ICS. In order to find the combination of factors, on both protein and gene levels, with the highest correlation to ICS, a multivariate statistical calculation was performed. Our results indicate that SNPs in DNA repair genes (XRCC3(241) and XPD751) influence the ICS and together with the expression of EGFR, Hsp70, Bax, and Bcl-2, they could predict the cisplatin sensitivity of head and neck cancer cell lines (r=0.614, p andlt;= 0.001).

Keywords
epidermal growth factor receptor, Bax, Bcl-2, heat shock protein 70, DNA repair genes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21513 (URN)10.3892/ijmm_00000264 (DOI)
Available from: 2009-10-02 Created: 2009-10-02 Last updated: 2017-12-13
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