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Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck.

Henriksson E, Kjellén E, Baldetorp B, Bendahl PO, Borg A, Brun E, Mertens F, Ohlsson T, Rennstam K, Wennerberg J, Wahlberg P - J. Exp. Clin. Cancer Res. (2009)

Bottom Line: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test.No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity.However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otorhinolaryngology, University Hospital Malmö, SE-205 02 Malmö, Sweden. Eva.Henriksson@skane.se

ABSTRACT

Background: The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24-35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers.The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status.

Methods: Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test (crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry.

Results: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake.

Conclusion: In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.

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Related in: MedlinePlus

The 18F-FDG uptake, expressed as counts per minute adjusted for time, versus number of viable cells present for the six cell lines, scatter plot and fitted regression lines.
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Figure 2: The 18F-FDG uptake, expressed as counts per minute adjusted for time, versus number of viable cells present for the six cell lines, scatter plot and fitted regression lines.

Mentions: The 18F-FDG uptake, expressed as counts per minute (cpm) adjusted for time, was strongly correlated with the number of viable cells present, as illustrated in Figure 2. The correlations varied between 0.94 (LU-HNSCC 3) and 0.99 (LU-HNSCC 7). The hypothesis of no difference in 18F-FDG uptake between the cell lines was evaluated in a linear regression framework (see Statistics) and according to this model, the predicted 18F-FDG uptake for 1,000,000 viable cells varied more than a factor 2, from 65,000 cpm for LU-HNSCC 3 to 133,000 cpm for LU-HNSCC 6. The hypothesis of equal 18F-FDG uptake for this fixed number of viable cells could be rejected (p < 0.0001; F-test). Significant differences in 18F-FDG uptake between the cell lines (p < 0.01) was seen for all reference values from 50,000 to 1,500,000 viable cells and also in sub-group analyses excluding one of the two cell lines with non-overlapping ranges for number of viable cells.


Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck.

Henriksson E, Kjellén E, Baldetorp B, Bendahl PO, Borg A, Brun E, Mertens F, Ohlsson T, Rennstam K, Wennerberg J, Wahlberg P - J. Exp. Clin. Cancer Res. (2009)

The 18F-FDG uptake, expressed as counts per minute adjusted for time, versus number of viable cells present for the six cell lines, scatter plot and fitted regression lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654548&req=5

Figure 2: The 18F-FDG uptake, expressed as counts per minute adjusted for time, versus number of viable cells present for the six cell lines, scatter plot and fitted regression lines.
Mentions: The 18F-FDG uptake, expressed as counts per minute (cpm) adjusted for time, was strongly correlated with the number of viable cells present, as illustrated in Figure 2. The correlations varied between 0.94 (LU-HNSCC 3) and 0.99 (LU-HNSCC 7). The hypothesis of no difference in 18F-FDG uptake between the cell lines was evaluated in a linear regression framework (see Statistics) and according to this model, the predicted 18F-FDG uptake for 1,000,000 viable cells varied more than a factor 2, from 65,000 cpm for LU-HNSCC 3 to 133,000 cpm for LU-HNSCC 6. The hypothesis of equal 18F-FDG uptake for this fixed number of viable cells could be rejected (p < 0.0001; F-test). Significant differences in 18F-FDG uptake between the cell lines (p < 0.01) was seen for all reference values from 50,000 to 1,500,000 viable cells and also in sub-group analyses excluding one of the two cell lines with non-overlapping ranges for number of viable cells.

Bottom Line: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test.No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity.However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otorhinolaryngology, University Hospital Malmö, SE-205 02 Malmö, Sweden. Eva.Henriksson@skane.se

ABSTRACT

Background: The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24-35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers.The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status.

Methods: Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test (crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry.

Results: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake.

Conclusion: In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.

Show MeSH
Related in: MedlinePlus