| 1. |
- Kjellström, Johan, et al.
(författare)
-
Increased toxicity of a trinuclear Pt-compound in a human squamous carcinoma cell line by polyamine depletion
- 2012
-
Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Mononuclear platinum anticancer agents hold a pivotal place in the treatment of many forms of cancers, however, there is a potential to improve response to evade resistance development and toxic side effects. BBR3464 is a promising trinuclear platinum anticancer agent, which is a polyamine mimic. The aim was to investigate the influence of polyamine pool reduction on the cytotoxic effects of the trinuclear platinum complex BBR3464 and cisplatin. Polyamine pool reduction was achieved by treating cells with either the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) or the polyamine analogue N-1,N-11-diethylnorspermine (DENSPM). Methods: A human squamous cell carcinoma cell line, LU-HNSCC-4, established from a primary head and neck tumour was used to evaluate cellular effects of each drug alone or combinations thereof. High-performance liquid-chromatography was used to quantify intracellular polyamine contents. Inductively coupled mass spectroscopy was used to quantify intracellular platinum uptake. Cells were exposed to DFMO or DENSPM during 48 h at concentrations ranging from 0 to 5 mM or 0 to 10 mu M, respectively. Thereafter, non-treated and treated cells were exposed to cisplatin or BBR3464 during 1 h at concentrations ranging from 0 to 100 mu M. A 96-well assay was used to determine cytotoxicity after five days after treatment. Results: The cytotoxic effect of BBR3464 on LU-HNSCC-4 cells was increased after cells were pre-treated with DENSPM or DFMO, and the interaction was found to be synergistic. In contrast, the interaction between cisplatin and DFMO or DENSPM was near-additive to antagonistic. The intracellular levels of the polyamines putrescine and spermidine were decreased after treatment with DFMO, and treatment with DENSPM resulted in an increase in putrescine level and concomitant decrease in spermidine and spermine levels. The uptake of BBR3464 was significantly increased after pre-treatment of the cells with DFMO, and varied dependent on the concentration of DENSPM. The uptake of cisplatin was unchanged. Conclusions: Taken together, these results demonstrate that combinations of polyamine synthesis inhibitors with BBR3464 appear to be a promising approach to enhance the anticancer activity against HSCC.
|
|
| 2. |
- Lindgren, Gustaf, et al.
(författare)
-
Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma.
- 2014
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.
|
|
| 3. |
- Wennerberg, Erik, et al.
(författare)
-
Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells
- 2014
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 20:22, s. 5733-5744
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.EXPERIMENTAL DESIGN: We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.RESULTS: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.CONCLUSIONS: ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy.
|
|
| 4. |
- Anderud, Jonas, et al.
(författare)
-
Guided bone augmentation using a ceramic space-maintaining device
- 2014
-
Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology. - : Elsevier. - 2212-4403 .- 2212-4411. ; 118:5, s. 532-538
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. The purpose of this study was to evaluate 3-dimensionally whether vertical bone augmentation can be achieved using a hollow hydroxyapatite space-maintaining device in a rabbit calvarial model. Furthermore, different inner surface topographies, different permeabilities, and different porosities of the ceramic were tested to determine the optimal conditions for bone regeneration.
|
|
| 5. |
- Annertz, Karin, et al.
(författare)
-
Alpha B-crystallin - a validated prognostic factor for poor prognosis in squamous cell carcinoma of the oral cavityl
- 2014
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 134:5, s. 543-550
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Alpha B-crystallin was found to be an independent prognostic marker for poor prognosis in oral cavity tumours. For oropharyngeal cancer, alpha B-crystallin had no prognostic value. Objective: The aim of this study was to see if earlier findings of alpha B-crystallin as an independent prognostic marker, and SPARC/osteonectin, PAI-1 and uPA as a prognostic combination for poor outcome in squamous cell carcinoma (SCC) of the head and neck could be confirmed in a new set of tumours. Methods: In a consecutive series of patients, assessed and primarily treated at a tertiary referral centre, histological sections from 55 patients with oral and SCC (OOPHSSC) with complete clinical data and follow-up were obtained. Oral and oropharyngeal tumours were studied separately. Immunohistochemical detection of alpha B-crystallin, SPARC/osteonectin, PAI-1 and uPA expression was performed. Results: Thirty-five patients had an oral tumour and 20 patients an oropharyngeal tumour. Twenty-five oral tumours stained negatively and 10 positively for alpha B-crystallin. For oropharyngeal tumours the figures were 15 negatively and 5 positively. Median disease-specific survival (DSS) for both sites was 33.8 and 11.9 months, for negative and positive alpha B-crystallin staining, respectively (p=0.046). For the oral cavity, median DSS was 27.3 months for negative tumours and 7.5 months for positive tumours (p=0.012). Corresponding figures for oropharyngeal tumours were 33.8 and 34.1 months (p=0.95). Thus, significance in survival was only found in oral cavity tumours. In multivariate analyses there were no significant differences in DSS in the oropharyngeal group when adjusted for tumour size (T status) and presence of neck node metastasis (N status). In the oral cavity group, the significantly better DSS for negative tumours became even stronger when adjusted for T and N status. No statistical difference was found in DSS between positive and negative staining for SPARC/osteonectin, PAI-1 or uPA.
|
|
| 6. |
- Annertz, Karin, et al.
(författare)
-
High-risk HPV and survival in patients with oral and oropharyngeal squamous cell carcinoma : 5-year follow up of a population-based study
- 2014
-
Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 8:134, s. 843-851
-
Tidskriftsartikel (refereegranskat)abstract
- CONCLUSION: No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. OBJECTIVES: To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. METHODS: A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000-2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. RESULTS: Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.
|
|
| 7. |
- Annertz, Karin, et al.
(författare)
-
The increase in incidence of cancer of the tongue in the Nordic countries continues into the twenty-first century
- 2012
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 132:5, s. 552-557
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusion: This study shows a persistent trend of an increase in the incidence of carcinoma of the tongue into the twenty-first century for both sexes and all age groups except for young males. Objectives: During the last decades increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been reported. We previously showed an increased incidence in SCC of the tongue in Scandinavia in 1960-1994, most pronounced in patients aged 20-39 years. The aim of this study was to investigate whether the trend of increased incidence of tongue cancer continued into the twenty-first century in a population-based study in the Nordic countries. Methods: Data for all reported SCCs of the tongue and base of tongue in patients aged 20-79 years during 1960-2008 were extracted from the NORDCAN registry, based on the National Cancer registries in the Nordic countries. Data from Sweden, Norway, Finland, Denmark, and Iceland were analyzed. The age groups 20-39, 40-64, and 65-79 years were studied separately as well as male and female figures. Results: In all, 12 280 cases were reported, of which 673 were diagnosed in patients aged 20-39 years. The trend of an increase persisted after 1994 in both sexes and all three age groups except in young males.
|
|
| 8. |
- Aplander, Karolina, et al.
(författare)
-
Entropy-Controlled and Enantiodivergent Lewis Acid Catalysis in Water
- 2012
-
Ingår i: Synthesis. - : Georg Thieme Verlag KG. - 0039-7881 .- 1437-210X. ; 44:6, s. 848-856
-
Tidskriftsartikel (refereegranskat)abstract
- Developing new and useful methods in asymmetric catalysis is of continuous importance. A current challenge is to address the imperatives of green chemistry, such that processes maximize resource-efficiency and minimize the generation of waste. To this end, this article discloses the potential of alpha-amino acids in the development of entropy-controlled and enantiodivergent Lewis acid catalysis. In an ytterbium-catalyzed aqueous Michael addition reaction, natural alpha-amino acids induced not only a large rate acceleration, but also an unusual and remarkable reversed temperature effect on enantioselectivity. As demonstrated with 17 alpha-amino acids, the enantioselectivity of the reaction can be significantly altered, and even reversed, simply by modifying the reaction temperature. After determining differential thermodynamic activation parameters, it was revealed that an unusually large entropy contribution was responsible for the observed effects. By further correlation to the influence of the aqueous medium, we put forward the concept of stereospecific aqueous solvation (SAS), which describes the bearing of aqueous solvation on the equilibrium of diastereomeric transition states, and thus on the R/S ratio of the product.
|
|
| 9. |
- Bjurberg, Maria, et al.
(författare)
-
Early metabolic flare in squamous cell carcinoma after chemotherapy is a marker of treatment sensitivity in vitro
- 2010
-
Ingår i: Nuclear medicine and molecular imaging. - : Springer. - 1869-3474 .- 1869-3482. ; 44:3, s. 165-169
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Early metabolic response with a decrease in glucose demand after cytotoxic treatment has been reported to precede tumor volume shrinkage. However, preclinical studies report of a very early rise in metabolism, a flare, following treatment. To elucidate these observations, we performed an experimental study on early metabolic response with sequential analysis of metabolic changes. Methods Three squamous cell carcinoma cell lines and one nontumorigenic cell line were exposed to cisplatin. The uptake of the fluorescent glucose analogue 2-NBDG was examined at days 1-6 using fluorescence microscopy. The relation between 2-NBDG-uptake and cell survival was evaluated. Results The tumor cells exhibited a high uptake of 2-NBDG, whereas the uptake in the nonmalignant cells was low. The more cisplatin sensitive cell lines exhibited a more pronounced metabolic flare than the less sensitive cell line. Conclusion A metabolic flare was a very early sign of treatment response and potentially it could be used as an early marker of treatment sensitivity.
|
|
| 10. |
- Cecchinato, Francesca, et al.
(författare)
-
In vitro evaluation of human fetal osteoblast response to magnesium loaded mesoporous TiO2 coating.
- 2014
-
Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 102:11, s. 3862-3871
-
Tidskriftsartikel (refereegranskat)abstract
- This work aimed to evaluate the in vitro response of Transfected Human Foetal Osteoblast (hFOB) cultured on a magnesium-loaded mesoporous TiO2 coating. The application of mesoporous films on titanium implant surfaces has shown very promising potential to enhance osseointegration. This type of coating has the ability to act as a framework to sustain bioactive agents and different drugs. Magnesium is the element that, after calcium, is the most frequently used to dope titanium implant surfaces, since it is crucial for protein formation, growth factor expression, and aids for bone mineral deposition on implant surfaces. Mesoporous TiO2 films with an average pore-size of 6 nm were produced by the evaporation-induced self-assembly method (EISA) and deposited onto titanium discs. Magnesium loading was performed by soaking the mesoporous TiO2 discs in a magnesium chloride solution. Surface characterization was conducted by SEM, XPS, optical interferometry, and AFM. Magnesium release profile was assessed at different time points using a Magnesium Detection kit. Cell morphology and spreading were observed with SEM. The cytoskeletal organization was stained with TRITC-conjugated Phalloidin and cell viability was evaluated through a mitochondrial colorimetric (MTT) assay. Furthermore, gene expression of bone markers and cell mineralization were analyzed by real time RT-PCR and alizarin-red staining, respectively. The surface chemical analysis by XPS revealed the successful adsorption of magnesium to the mesoporous coating. The AFM measurements revealed the presence of a nanostructured surface roughness. Osteoblasts viability and adhesion as well as the gene expression were unaffected by the addition of magnesium possibly due to its rapid burst release, however, were enhanced by the 3D nanostructure of the TiO2 layer.
|
|
