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Thunell, Lena
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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
Åpne denne publikasjonen i ny fane eller vindu >>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 (engelsk)Inngår i: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 31, s. 64-72Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Elsevier, 2015
Emneord
Head and neck squamous cell carcinoma; XPC; XPD; HPV; p53; Overall survival
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-120212 (URN)10.1016/j.dnarep.2015.05.003 (DOI)000357138600007 ()26001739 (PubMedID)
Merknad

Funding Agencies|Swedish Cancer Society; Laryngfonden

Tilgjengelig fra: 2015-07-21 Laget: 2015-07-20 Sist oppdatert: 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
Åpne denne publikasjonen i ny fane eller vindu >>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 (engelsk)Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 51, nr 1, s. 24-30Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Elsevier, 2015
Emneord
Head and neck cancer; Radiotherapy; Predictive factors; Survivin; WRAP53
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-113161 (URN)10.1016/j.oraloncology.2014.10.003 (DOI)000346210900007 ()25456005 (PubMedID)
Merknad

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

Tilgjengelig fra: 2015-01-14 Laget: 2015-01-12 Sist oppdatert: 2017-12-05
Stjernstrom, A., Karlsson, C., Fernandez, O. J., Söderkvist, P., Karlsson, M. G. & Thunell, L. (2014). Alterations of INPP4B, PIK3CA and pAkt of the PI3K pathway are associated with squamous cell carcinoma of the lung. Cancer Medicine, 3(2), 337-348
Åpne denne publikasjonen i ny fane eller vindu >>Alterations of INPP4B, PIK3CA and pAkt of the PI3K pathway are associated with squamous cell carcinoma of the lung
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2014 (engelsk)Inngår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 3, nr 2, s. 337-348Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The aim of the study was to investigate how alterations in the PI3K pathway correlate with non-small cell lung cancer subtypes squamous cell carcinoma (SSC) and adenocarcinoma (ADCA). We analyzed copy number variation and protein expression of INPP4B, protein expression of pAkt, PDPK1, and PTEN and mutational status of PIK3CA and PTEN in 180 cases. Nineteen% displayed loss of INPP4B copy, whereas 47% lacked expression, both showing correlation with SCC. Elevated pAkt expression was seen in 63% of all cases, also correlating to SCC. PDPK1 was expressed in 70%, more in male than female patients. Regarding PTEN, 50% displayed loss of expression, of which seven were identified with mutations in the phosphatase domain. We detected nine cases (5%) of PIK3CA mutations, all identified as the E545K hot spot mutation in the helical domain, all except one in SCC. When analyzing all PI3K pathway components together, we show that patients with at least one alteration in the PI3K pathway are twice as likely to have SCC, than ADCA. Interestingly, we also found a strong correlation between high pAkt expression and PTEN expression. As comparison, we also analyzed mitogen-activated protein kinase (MAPK) pathway genes, where we identified fifteen KRAS mutations (8%) and one BRAF mutation (1%), significantly associated to ADCA. No association was found to the Gly972Arg polymorphism of IRS-1, involved in activation of both PI3K and MAPK pathways. In conclusion, we show here that several components of the PI3K pathway, alone and in combination, are correlated to development of SCC of the lung.

sted, utgiver, år, opplag, sider
Wiley Open Access, 2014
Emneord
INPP4B; MAPK pathway; non-small cell lung cancer; PI3K; squamous cell carcinoma
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-114455 (URN)10.1002/cam4.191 (DOI)000348220600013 ()24500884 (PubMedID)
Merknad

Funding Agencies|Swedish Cancer Society; Petrus and Augusta Hedlunds Foundation; Medical Research Committee of the County Council in Ostergotland

Tilgjengelig fra: 2015-02-20 Laget: 2015-02-20 Sist oppdatert: 2017-12-04
Thunell, L., Bivik, C., Wäster, P., Fredrikson, M., Stjernstrom, A., Synnerstad, I., . . . Enerbäck, C. (2014). MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma. Melanoma research, 24(3), 190-197
Åpne denne publikasjonen i ny fane eller vindu >>MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma
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2014 (engelsk)Inngår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 24, nr 3, s. 190-197Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The p53 pathway regulates stress response, and variations in p53, MDM2, and MDM4 may predispose an individual to tumor development. The aim of this study was to study the impact of genetic variation on sporadic and hereditary melanoma. We have analyzed a combination of three functionally relevant variants of the p53 pathway in 258 individuals with sporadic malignant melanomas, 50 with hereditary malignant melanomas, and 799 healthy controls. Genotyping was performed by PCR-restriction fragment length polymorphism, pyrosequencing, and allelic discrimination. We found an increased risk for hereditary melanoma in MDM2 GG homozygotes, which was more pronounced among women (P=0.035). In the event of pairwise combinations of the single nucleotide polymorphisms, a risk elevation was shown for MDM2 GG homozygotes/p53 wild-type Arg in hereditary melanoma (P=0.01). Individuals with sporadic melanomas of the superficial spreading type, including melanoma in situ, showed a slightly higher frequency of the MDM2 GG genotype compared with those with nodular melanomas (P=0.04). The dysplastic nevus phenotype, present in the majority of our hereditary melanoma cases and also in some sporadic cases, further enhanced the effect of the MDM2 GG genotype on melanoma risk (P=0.005). In conclusion, the results show an association between MDM2 SNP309 and an increased risk for hereditary melanoma, especially among women. Analysis of sporadic melanoma also shows an association between MDM2 and the superficial spreading melanoma subtype, as well as an association with the presence of dysplastic nevi in sporadic melanoma.

sted, utgiver, år, opplag, sider
Lippincott, Williams andamp; Wilkins, 2014
Emneord
superficial spreading melanoma; MDM2; hereditary melanoma; MDM4; p53; dysplastic nevi
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-107446 (URN)10.1097/CMR.0000000000000063 (DOI)000335683500002 ()
Tilgjengelig fra: 2014-06-12 Laget: 2014-06-12 Sist oppdatert: 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
Åpne denne publikasjonen i ny fane eller vindu >>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 (engelsk)Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, nr 8, s. 1994-2003Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Wiley-Blackwell, 2013
Emneord
head and neck tumors, radiotherapy, survivin, single nucleotide polymorphism
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-97229 (URN)10.1002/ijc.28200 (DOI)000322908600025 ()
Merknad

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||

Tilgjengelig fra: 2013-09-06 Laget: 2013-09-05 Sist oppdatert: 2017-12-06
Jakobsen Falk, I., Khan, M. S., Thunell, L., Nahi, H. & Green, H. (2012). Association of CYP2B6 Genotype with Survival and Progression Free Survival in Cyclophosphamide Treated Multiple Myeloma. Journal of Cancer Therapy, 3(1), 20-27
Åpne denne publikasjonen i ny fane eller vindu >>Association of CYP2B6 Genotype with Survival and Progression Free Survival in Cyclophosphamide Treated Multiple Myeloma
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2012 (engelsk)Inngår i: Journal of Cancer Therapy, ISSN 2151-1934, E-ISSN 2151-1942, Vol. 3, nr 1, s. 20-27Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective: Cyclophosphamide is a conventional pro-drug used in Multiple Myeloma (MM) and other malignancies. The highly polymorphic CYP2B6 is suggested as a major contributor in cyclophosphamide bioactivation, and GST en-zymes are involved in detoxification. Polymorphisms of these enzymes may affect enzyme expression and function as well as treatment outcome. The aim of this study was to investigate the impact of the CYP2B6 SNPs G516T, A785G and C1459T, GSTP1 SNP Ile105Val, and GSTM1 and GSTT1 null variants, on the outcome for cyclophosphamide treated MM patients, in order to find markers of value for individualised therapy. Methods: We used allele specific PCR and Pyrosequencing to investigate the impact of CYP2B6 SNPs G516T, A785G and C1459T, GSTP1 Ile105Val, and GSTM1 and GSTT1 variants, on the outcome for 26 cyclophosphamide treated multiple myeloma patients. Results and Major Conclusion:

The CYP2B6 785G carriers had significantly shorter progression free survival (p = 0.048*) and overall survival (p = 0.037*) with 785G/G patients having the worst outcome compared to patients carrying the wild type. A shorter progression free survival was also indicated in patients carrying both CYP2B6 516T & 785G (p = 0.068). These results indicate a predictive role of CYP2B6 SNPs, particularly A785G, in cyclophosphamide treatment.

sted, utgiver, år, opplag, sider
Scientific Research Publishing, 2012
Emneord
Multiple Myeloma; Cyclophosphamide; CYP2B6; Glutathion-S-Transferases (GST); Single Nucleotide Polymorphisms; Pharmacogenetics; Pyrosequencing
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-76109 (URN)10.4236/jct.2012.31003 (DOI)
Tilgjengelig fra: 2012-03-27 Laget: 2012-03-27 Sist oppdatert: 2017-12-07
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
Åpne denne publikasjonen i ny fane eller vindu >>Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines
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2011 (engelsk)Inngår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 40, nr 10, s. 739-746Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
John Wiley and sons, 2011
Emneord
head and neck tumors, radiotherapy, survivin, Bcl-2 family, p53 Arg72Pro
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-61585 (URN)10.1111/j.1600-0714.2011.01036.x (DOI)000296607200002 ()
Merknad
Funding agencies|Swedish Laryng Foundation||County Council of Ostergotland (OLL)||Swedish Cancer Foundation||Foundation of Olle Engkvist||Linkoping University Hospital||Tilgjengelig fra: 2010-11-16 Laget: 2010-11-16 Sist oppdatert: 2017-12-12bibliografisk kontrollert
Djerf, E., Trinks, C., Abdiu, A., Thunell, L., Hallbeck, A.-L. & Walz, T. M. (2009). ErbB receptor tyrosine kinases contribute to proliferation of malignant melanoma cells: inhibition by gefitinib (ZD1839). Melanoma research, 19(3), 156-166
Åpne denne publikasjonen i ny fane eller vindu >>ErbB receptor tyrosine kinases contribute to proliferation of malignant melanoma cells: inhibition by gefitinib (ZD1839)
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2009 (engelsk)Inngår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, ISSN 0960-8931, Vol. 19, nr 3, s. 156-166Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Members of the epidermal growth factor (EGF) family of structurally related tyrosine kinase receptors, known as the ErbB receptors (EGFR/ErbB1/HER1, ErbB2/HER2/neu, ErbB3/HER3 and ErbB4/HER4) and their respective ligands, have been suggested to be involved in the development and progression of malignant melanoma. Here we investigate the effects of the ErbB1 tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) on human malignant melanoma cells (RaH3 and RaH5) in vitro. ZD1839 inhibited proliferation of exponentially growing RaH3 and RaH5 cells in a dose-dependent manner with a half-maximally effective dose of 3.5 and 2.0 mu mol/l, respectively. Cell growth was inhibited at 0.1 mu mol/l ZD1839 in both cell lines. Maximal inhibition was accomplished at 10 mu mol/l ZD1839; however, the effect was not complete as both cell lines showed a continuous slow growth during the treatment period. Flow cytometry analysis of cell-cycle distribution showed that ZD1839 treatment caused accumulation of RaH3 and RaH5 cells in the G, phase. The growth arrest induced by ZD1839 coincided with upregulation of the cyclin-dependent kinase inhibitor p27(KIP1). There was no increase in apoptosis as determined by analysis of plasma phosphatidyl serine redistribution. Western blot analysis revealed that ZD1839 substantially reduced tyrosine phosphorylation of ErbB1 as well as ErbB2 and ErbB3. This was accompanied by a concomitant decrease in Akt-phosphorylation, Erk1/2-phosphorylation, and Stat3-phosphorylation. Our results show that ZD1839 interferes with the growth of human malignant melanoma cells by cytostatic effects. These findings indicate the possible use of ErbB receptor kinase inhibitors as a novel treatment strategy in malignant melanoma.

Emneord
antiproliferative, ErbB receptors, gefitinib, melanoma, tyrosine kinase inhibitor
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-19129 (URN)10.1097/CMR.0b013e32832c6339 (DOI)
Tilgjengelig fra: 2009-06-12 Laget: 2009-06-12 Sist oppdatert: 2017-12-13bibliografisk kontrollert
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
Åpne denne publikasjonen i ny fane eller vindu >>Polymorphism of FGFR4 in cancer development and sensitivity to cisplatin and radiation in head and neck cancer
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2009 (engelsk)Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 45, nr 1, s. 23-29Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Elsevier, 2009
Emneord
Oral tumours, Radiotherapy, Chemotherapy
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-16724 (URN)10.1016/j.oraloncology.2008.03.007 (DOI)000262607900005 ()18487077 (PubMedID)
Tilgjengelig fra: 2009-02-14 Laget: 2009-02-13 Sist oppdatert: 2017-12-14bibliografisk kontrollert
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
Åpne denne publikasjonen i ny fane eller vindu >>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 (engelsk)Inngår i: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 24, nr 4, s. 549-556Artikkel i tidsskrift (Fagfellevurdert) 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).

Emneord
epidermal growth factor receptor, Bax, Bcl-2, heat shock protein 70, DNA repair genes
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-21513 (URN)10.3892/ijmm_00000264 (DOI)
Tilgjengelig fra: 2009-10-02 Laget: 2009-10-02 Sist oppdatert: 2017-12-13
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