| 1. |
- Fernö, Mårten, et al.
(författare)
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Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay
- 1996
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 32a:5, s. 793-801
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Tidskriftsartikel (refereegranskat)abstract
- Urokinase plasminogen activator (uPA) is involved in the activation of different proteases which participate in the degradation of extracellular matrix, thereby enhancing the invasive capacity of tumour cells. uPA has been shown to be of prognostic importance in breast cancer. We have analysed uPA with a new luminometric immunoassay (LIA), applicable in cytosol samples routinely used for oestrogen-receptor (ER) and progesterone-receptor (PgR) analyses. At a cut-off value of 0.62 ng uPA/mg protein, 33% (230/688) samples were classified as representing high uPA tumours. High uPA content was found to be associated with shorter recurrence-free survival (median observation time: 42 months), ER and PgR negativity, increased p53 expression, DNA non-diploidy and a high S-phase fraction (SPF), but not with lymph node involvement or tumour size (< or = 20 mm versus > 20 mm). In the subgroup of patients not treated with systemic adjuvant therapy, multivariate analysis showed uPA to be an independent prognostic factor together with lymph node status and SPF. If these results can be reproduced, uPA may be a factor suitable for inclusion in a prognostic index.
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| 2. |
- Kjellén, Elisabeth, et al.
(författare)
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A Phase I/II Evaluation of Metoclopramide as a Radiosensitiser in Patients with Inoperable Squamous Cell Carcinoma of the Lung
- 1995
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 31:13-14, s. 2196-2202
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.
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| 3. |
- Gentile, Massimiliano, et al.
(författare)
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p53 and survival in early onset breast cancer : analysis of gene mutations, loss of heterozygosity and protein accumulation
- 1999
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 35:8, s. 1202-1207
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Tidskriftsartikel (refereegranskat)abstract
- The p53 protein has proven to be central in tumorigenesis by its cell cycle regulatory properties and both gene mutations and protein accumulation have been associated with poor prognosis in breast cancer. The present study was undertaken to investigate the prognostic significance of gene mutations, p53 protein accumulation and of loss of heterozygosity (LOH) at the TP53 locus in young (age <37 years) breast cancer patients. In total, gene mutations were found in 21 of the 123 patients (17%), LOH in 20 of the 47 informative cases (43%) and protein accumulation in 47 of the 102 available cases (46%). Log rank analysis revealed no significant association between survival and TP53 mutations (in general), p53 protein accumulation or LOH. However, missense mutations localised to the zinc binding domain were significantly (P=0.0007) associated with poorer prognosis. As indicated in this as well as other studies, p53 protein accumulation is frequently found in young breast cancer patients, but this protein overexpression appears to be of minor significance for survival. Nevertheless, the present report also suggests that specific mutations contribute substantially to tumour aggressiveness.
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| 4. |
- Nordén, T, et al.
(författare)
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Mammographic screening for breast cancer : What cancers do we find?
- 1997
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 33:4, s. 624-628
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare lymph node involvement of breast cancer cases detected at mammography screening with clinically-detected cases. During a 3-year period, 273 primary breast cancers were detected in a population-based screening programme, and 149 primary breast cancers were diagnosed clinically. Lymph node involvement was evaluated in univariate and multivariate logistic regression models correcting for tumour size, histological grade, steroid receptor status and DNA-ploidy. Patients with screen-detected cancers had a low relative risk of having lymph node metastases (univariate, OR = 0.31; 95% confidence interval = 0.19-0.52). In the multivariate logistic regression model, the relative risk was halved (OR = 0.47; 0.28-0.78). The reduced risk was more pronounced for women younger than 50 years of age compared to older women. The risk for screen-detected cases of having lymph node metastases at diagnosis was statistically significantly lower than for clinically-detected cases. The marked reduction, even when correcting for tumour size, makes it less likely that factors such as detection of clinically innocent tumours, length bias sampling or clinical symptoms related to axillary metastases can explain the whole difference. The results indicate at least part of the effect may be explained by tumour progression in the late preclinical detectable phase.
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| 5. |
- Norrback, Karl-Fredrik, et al.
(författare)
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Telomeres and telomerase in normal and malignant haematopoietic cells
- 1997
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 33:5, s. 774-780
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Tidskriftsartikel (refereegranskat)abstract
- The normal haematopoietic system harbours telomerase-competent cells with a capacity to upregulate the activity to notable levels in a telomere length-independent manner. Strong telomerase activity is found in progenitor stem cells and activated lymphocytes in vitro as well as in vivo, indicating that cells with high growth requirements can readily upregulate telomerase. Despite detection of telomerase activity, a gradual telomere erosion occurs in stem cells and lymphocytes, with significantly shortened telomeres at higher ages, a phenomenon that might be of importance for developing immunosenescence and exhausted haematopoiesis. In malignant haematopoietic disorders telomerase activity is a general finding with large differences in activity levels. The strongest telomerase expression has been shown in acute leukaemias and non-Hodgkin's lymphomas, especially high grade cases. There are indications that the level of activity might parallel tumour progression and be of prognostic relevance, but studies of larger patient materials are needed. An association between the cell cycle and telomerase activity exists, especially for normal haematopoietic cells, and induction of a differentiation programme in immortalised cell lines downregulates telomerase activity. The expression of telomerase activity seems to be regulated at different levels, since for immature bone marrow cells the level of activity seemed to parallel better the phenotype than the proliferation state. The frequent expression of telomerase in leukaemias and lymphomas makes these disorders interesting targets for future anti-telomerase therapy.
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| 6. |
- Påhlman, S., et al.
(författare)
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Differentiation and survival influences of growth factors in human neuroblastoma
- 1995
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 31A:4, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- Human neuroblastoma cell lines are established from high-stage, highly malignant tumours. Despite this and the fact that these tumours are arrested at an early, immature stage, many cell lines have the capacity to undergo neuronal differentiation under proper growth conditions. One such cell line is the noradrenergic SH-SY5Y cell line. These cells can be induced to mature by a variety of modalities, resulting in different mature phenotypes. The use of this cell system as a model to study the stem cell character of neuroblastoma is reviewed and discussed. In particular, we focus on growth factor dependencies in the SH-SY5Y system, and compare that to the normal situation, i.e. growth factor control of sympathetic neuronal and neuroendocrine differentiation during human and rat embryogenesis.
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| 7. |
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| 8. |
- Wu, F., et al.
(författare)
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A mechanism behind the antitumour effect of 6-diazo-5-oxo-L-norleucine (DON) : Disruption of mitochondria
- 1999
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 35:7, s. 1155-1161
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Tidskriftsartikel (refereegranskat)abstract
- 6-diazo-5-oxo-l-norleucine (DON) exerts a growth inhibitory effect selectively on the neuroendocrine tumour cell line BON and is proposed as an antitumour drug. The mechanism behind this has not yet been clarified. In the present study, transmission electron microscopy was used for the assessment of changes in cellular organelles. Furthermore, the methylthiazolyldiphenyl tetrazolium (MTT) assay for mitochondrial enzymatic activity, a fluorescent marker (rhodamine 123) for mitochondrial integrity and [2-11C]-acetyl-carnitine which is a substrate of the tricarboxylic acid cycle of mitochondria were employed. The studies were performed in parallel in BON and in a neuroblastoma cell line LAN, with the cells grown as monolayers or as multicellular aggregates. Severe morphological changes of intracellular organelles were observed in BON aggregates treated with low-doses of DON. Especially striking was the disruption of mitochondrial internal membrane structures. Other features included the swelling of endoplasmic reticulum, autophagocytosis of secretory granules and nuclear condensation (apoptosis). In LAN cells, no ultrastructural changes were seen after DON treatment. The MTT assay indicated inhibition of mitochondrial enzymatic activity in BON cells but not in LAN cells after 5 h treatment with DON. The mitochondrial damage was also demonstrated as a reduced metabolism of [2-11C]-acetyl-carnitine. The observations revealed mitochondrial damage by DON treatment and suggest that the mitochondria might be a primary target for the antitumour effect in neuroendocrine cells.
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| 9. |
- Zhang, Hong, et al.
(författare)
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K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa.
- 1998
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 34:13, s. 2053-2057
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Tidskriftsartikel (refereegranskat)abstract
- The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas. K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69 (6%) of transitional mucosa samples, but not in the normal mucosa. Further, mutation rates were increased in younger patients (P = 0.001) and in mucinous carcinomas (50%) compared with well differentiated (17%), moderately differentiated (26%) or poorly differentiated (24%) tumours. Our findings indicate that mucinous carcinoma may represent a distinct genetic entity.
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| 10. |
- Åvall-Lundqvist, Elisabeth, et al.
(författare)
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The impact of tumour angiogenesis, p53 overexpression and proliferative activity (MIB-1) on survival in squamous cervical carcinoma.
- 1997
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 33:11, s. 1799-1804
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Tidskriftsartikel (refereegranskat)abstract
- Tumour angiogenesis (antifactor VIII-related antigen antibody), p53 overexpression (DO-1) and proliferative activity (MIB-1) were immunohistochemically analysed for the prediction of long-term survival in 113 patients with squamous cervical carcinoma. The median follow-up time was 82 months (range 72-99). In early stages (IB-IIA), neovascularisation was significantly related to tumour size. Significantly more patients in stage IIA had high tumour vascularity compared to stage IB (P < 0.01) but no significant difference was found between early and advanced stages (IIB-IVB) of cervical carcinoma. p53 overexpression was correlated to the stage of disease (P < 0.01). No relationship was found between tumour angiogenesis, p53 overexpression or MIB-1 and pelvic lymph node metastases, histological subtype or differentiation. Tumours with more than 50% p53 overexpression was significantly correlated with survival in the univariate analysis, but no independent predictive value was found. It is concluded that immunohistochemically detectable p53 overexpression as measured by DO-1 and proliferative activity as measured by MIB-1 seems of no clinical value for the prediction of long-term survival in squamous cervical carcinoma. The predictive value of tumour angiogenesis for survival outcome has still to be determined in squamous cervical carcinoma.
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