| 1. |
- Brun, Eva, et al.
(author)
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Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas
- 2001
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 40:4, s. 491-496
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Journal article (peer-reviewed)abstract
- The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.
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| 2. |
- Brun, Ann, et al.
(author)
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Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells
- 2004
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 103:11, s. 4126-4133
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Journal article (peer-reviewed)abstract
- Enforced expression of Hoxb4 dramatically increases the regeneration of murine hematopoietic stem cells (HSCs) after transplantation and enhances the repopulation ability of human severe combined immunodeficiency (SCID) repopulating cells. Therefore, we asked what physiologic role Hoxb4 has in hematopoiesis. A novel mouse model lacking the entire Hoxb4 gene exhibits significantly reduced cellularity in spleen and bone marrow (BM) and a subtle reduction in red blood cell counts and hemoglobin values. A mild reduction was observed in the numbers of primitive progenitors and stem cells in adult BM and fetal liver, whereas lineage distribution was normal. Although the cell cycle kinetics of primitive progenitors was normal during endogenous hematopoiesis, defects in proliferative responses of BM Lin(-) Sca1(+) c-kit(+) stem and progenitor cells were observed in culture and in vivo after the transplantation of BM and fetal liver HSCs. Quantitative analysis of mRNA from fetal liver revealed that a deficiency of Hoxb4 alone changed the expression levels of several other Hox genes and of genes involved in cell cycle regulation. In summary, the deficiency of Hoxb4 leads to hypocellularity in hematopoietic organs and impaired proliferative capacity. However, Hoxb4 is not required for the generation of HSCs or the maintenance of steady state hematopoiesis.
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| 3. |
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| 4. |
- Brun, Eva, et al.
(author)
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FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
- 2002
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In: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
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Journal article (peer-reviewed)abstract
- BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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| 5. |
- Brun, Eva
(author)
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Head and Neck Cancer: Studies on microvessel density, radiation response and FDG PET
- 2001
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Doctoral thesis (other academic/artistic)abstract
- Treatment options of head and neck squamous cell carcinoma (HNSCC) usually include combinations of radiotherapy and surgery, and in some cases addition of chemotherapy. In locally advanced cases cure rates are low. Current prognostic factors cannot foresee the outcome for the individual patient. There is consequently a need for reliable prognostic and predictive factors. Through identification of such factors therapeutic interventions can be made early during therapy to increase tumour control and survival. In the present studies the association between microvessel density (MVD) in tumours and response to radiation has been explored. We have also studied the association between response to radiation and tumour metabolism, both prior to and during therapy (radical radiotherapy and in 10 cases also neoadjuvant chemotherapy). Metabolism was studied with a glucose analogue, FDG, and positron emission tomography, PET.The metabolic rate of FDG was compared to treatment outcome and survival and also to established tumour properties, as cell proliferation, tumourgrade and DNAcontent. Microvessel density showed a complex relation to radiation treatment response and outcome. Among patients with tumours manifesting complete response to radiotherapy MVD was above the lowest quartile of the MVDcounts according to computerised image analysis. In the subsequent study the relationship between higher MVD and response to radiotherapy could not be reproduced, when performed manually. High MVD within the epithelial tumour tissue, not in the tumour stroma, was then found to be an adverse prognostic factor, with a lower probability of local control and a higher rate of distant metastases.Tumour response evaluated histopathologically, after a preoperative radiation dose of 50 Gy was strongly correlated to outcome, regardless of the subsequent radical surgery.This implies that radiosensitivity per se is a strong prognostic marker. Tumour metabolism (FDG PET) was associated to therapy outcome. The pre treatment value was of limited prognostic value whereas the second PET, early during therapy, was associated to therapy outcome, in terms of complete response, local control and survival. When comparing the value of the metabolic rate (MR) to a simpler quantification, the standar-dised uptake value (SUV) of FDG, we found that MR was more strongly correlated to therapy outcome. Furthermore associations were found to be significant only for the primary tumours and not for node metastases. This implies a different pattern of response in node metastases compared to that of the corresponding primary tumour. There was no strong association between tumour metabolism and proliferation, DNA content or histologic grade. MR FDG reflects tumour aggressiveness. Repeated FDG studies during therapy are feasible and might justify therapeutic interventions in non-responders.
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| 6. |
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| 7. |
- Åkervall, Jan, et al.
(author)
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Cyclin D1 overexpression versus response to induction chemotherapy in squamous cell carcinoma of the head and neck--preliminary report
- 2001
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 40:4, s. 505-511
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate whether there is an association between overexpression of cyclin D1 and response to therapy. Immunohistochemical overexpression of cyclin D1 was determined in paraffin-embedded specimens from diagnostic biopsies of 89 primary cases of squamous cell carcinoma of the head and neck (SCCHN), using a polyclonal antiserum. The tumor response rates were estimated after curative treatment (i.e. surgery and/or radiotherapy and/or chemotherapy). Patients whose tumors were overexpressing cyclin D1 showed complete or partial response to neoadjuvant chemotherapy with cisplatin/5-FU. In addition, a majority of cyclin D1 negative tumors did not respond at all to this treatment (p = 0.02, Fisher's exact test). This study indicates that immunohistochemical assessment of cyclin D1 expression in SCCHN could be a new predictive marker to select a subgroup of patients that will benefit from neoadjuvant chemotherapy.
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