| 31. |
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| 32. |
- Nilsson, Ola, 1957, et al.
(author)
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Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth?
- 1992
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In: International journal of cancer. Journal international du cancer. - 0020-7136. ; 51:2, s. 195-203
-
Journal article (peer-reviewed)abstract
- The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF-I-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-I. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-I-immunoreactive component eluting in the position of rhIGF-I, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.
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| 33. |
- Tingström, Anders, et al.
(author)
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Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1
- 1992
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In: Journal of Cell Science. - 0021-9533. ; 102:2, s. 315-322
-
Journal article (peer-reviewed)abstract
- We have examined the effects of three macrophagederived cytokines, platelet-derived growth factor (PDGF), transforming growth factor-01 (TGF-01) and interleukin-1 a (IL-la) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-/J1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF Lsoforms. However, the stimulatory effect of TGF-/S1 was not affected by any of the anti-PDGF antibodies. The ability of PDGF to stimulate contraction became less pronounced in collagen gel cultures grown in the absence of growth factors over periods of several days. Under the same conditions, the stimulatory effect of TGF-/J1 was not reduced. The reduced response to PDGF may be due to reduced tension on fibroblasts growing in collagen gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF-BB-induced PDGF ^-receptor aggregates when compared to fibroblasts on attached collagen gels. LL-1 a inhibited initial collagen gel contraction, and at later stages induced a visible degradation of the collagen gels, presumably due to the generation of collagenase activity. The combination of IL-la and PDGF-BB stimulated initial collagen gel contraction, although less effectively than PDGF-BB alone. At later stages, collagen gel degradation was stimulated by this combination of cytokines. In contrast, the combination of IL-la and TGF-/51 did not stimulate collagen gel contraction, or any visible collagen gel degradation. Our data suggest that fibroblast-mediated collagen gel contraction can be modulated by cytokines via different mechanisms. Our data are of importance in the understanding of the modulatory roles of cytokines in connective tissue cell activities in inflammatory processes, such as wound healing.
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| 34. |
- Alling, Christer, et al.
(author)
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Muscarinic receptor-stimulated expression of c-fos in neuroblastoma cells
- 1994
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In: Alcohol and alcoholism. Supplement. - 1358-6173. ; :2, s. 103-108
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Journal article (peer-reviewed)abstract
- The intracellular signal cascade transducing muscarinic-receptor-stimulation to gene expression was investigated in human neuroblastoma SH-SY5Y cells. Naive and ethanol-exposed SH-SU5Y cells were stimulated with carbachol (CCh) and inositol 1,4-5-trisphosphate (IP3), 1,2-diacylglycerol (DAG), and c-fos mRNA levels were analyzed using a radioreceptor assay (IP3) thin-layer chromatography (DAG) and Northern blot (c-fos mRNA). Application of the muscarinic agonist CCh induced a rapid increase in (IP3), peaking within seconds after the CCh-addition. There was also an accumulation of DAG reaching maximum after 5 min of receptor-stimulation. Stimulation with CCh also induced expression of the immediate-early gene c-fos in these cells. These events were mediated via muscarinic M1 receptors and the inhibitory effects of H7, staurosporin, and RO31-7549 on the c-fos expression indicated that it was mediated via protein kinase C. Acute exposure to 100 mM ethanol inhibited the formation of IP3 and the expression of c-fos. These effects were due to an increase in the EC50 of CCh for the events. Exposure to 100 mM ethanol for 4 days caused a potentiation of these two events. The EC50 was unaffected but the maximal response was increased. These data indicate that this signal transduction system is inhibited by acute exposure to 100 mM ethanol, an effect that is compensated for after exposure to ethanol for 4 days.
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| 35. |
- Albin, Maria, et al.
(author)
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Mineral fibres, fibrosis, and asbestos bodies in lung tissue from deceased asbestos cement workers
- 1990
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In: British Journal of Industrial Medicine. - 0007-1072. ; 47:11, s. 767-774
-
Journal article (peer-reviewed)abstract
- Lung tissue from 76 deceased asbestos cement workers (seven with mesothelioma) exposed to chrysotile asbestos and small amounts of amphiboles, has been studied by transmission electron microscopy, together with lung tissue from 96 controls. The exposed workers with mesothelioma had a significantly higher total content of asbestos fibre in the lungs than those without mesothelioma, who in turn, had higher concentrations than the controls (medians 189, 50, and 29 x 10(6) fibres/g (f/g]. Chrysotile was the major type of fibre. The differences were most pronounced for the amphibole fibres (62, 4.7, and 0.15 f/g), especially crocidolite (54, 1.8 and less than 0.001 f/g), but were evident also for tremolite (2.9, less than 0.001, and less than 0.001 f/g) and anthophyllite (1.7, less than 0.001, and less than 0.001 f/g). For amosite, there was no statistically significant difference between lungs from workers with and without mesothelioma; the lungs of workers had, however, higher concentrations than the controls. Strong correlations were found between duration of exposure and content of amphibole fibres in the lungs. Asbestos bodies, counted by light microscopy, were significantly correlated with the amphibole but not with the chrysotile contents. Fibrosis was correlated with the tremolite but not the chrysotile content in lungs from both exposed workers and controls. Overall, similar results were obtained using fibre counts and estimates of mass.
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| 36. |
- Albin, Maria, et al.
(author)
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Mortality and cancer morbidity in cohorts of asbestos cement workers and referents
- 1990
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In: British Journal of Industrial Medicine. - 0007-1072. ; 47:9, s. 602-610
-
Journal article (peer-reviewed)abstract
- Total and cause specific mortality and cancer morbidity were studied among 1929 asbestos cement workers with an estimated median cumulative exposure of 2.3 fibre (f)-years/ml (median intensity 1.2 f/ml, predominantly chrysotile). A local reference cohort of 1233 industrial workers and non-case referents from the exposed cohort were used for comparisons. The risk for pleural mesothelioma was significantly increased (13 cases out of 592 deaths in workers with at least 20 years latency). No case of peritoneal mesothelioma was found. A significant dose response relation was found for cumulative exposure 40 years or more before the diagnosis, with a multiplicative relative risk (RR) of 1.9 for each f-year/ml. No relation was found with duration of exposure when latency was accounted for. There was a significant overrisk in non-malignant respiratory disease (RR = 2.6). The overall risks for respiratory cancer, excluding mesothelioma, and for gastrointestinal cancer were not significantly increased. Surprisingly, colorectal cancer displayed a clear relation with cumulative dose, with an estimated increase of 1.6% in the incidence density ratio for each f-year/ml (but not with duration of exposure).
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| 37. |
- Baldetorp, Bo, et al.
(author)
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Image cytometric DNA analysis in human breast cancer analysis may add prognostic information in diploid cases with low S-phase fraction by flow cytometry
- 1992
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In: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 13:6, s. 577-585
-
Journal article (peer-reviewed)abstract
- Measurements of DNA ploidy can be performed either with image cytometry (ICM) or flow cytometry (FCM); both methods provide independent prognostic information in primary breast cancer. The aim of the present investigation was to compare the two methods and to relate the findings to prognosis (median follow-up 42 months). Concordance in ploidy status (diploid, tetraploid, aneuploid) was obtained in 76% of the samples (168/222). When the fraction of S-phase cells (SPF) from FCM analysis was also taken into consideration, four different groups of samples were obtained (Flow I-IV), which were considered to correspond to the Auer classification (Auer I-IV) of DNA histograms obtained from image cytometry. Complete concordance between the two techniques now was 70% (155/222). Samples classified as Flow I (diploid or near-diploid with low SPF) and Auer I had a distant metastasis rate of 3/60 (5%), as compared to 62/154 (40%) for all other combinations of the Flow and Auer classifications taken together. Thus, the only findings of prognostic importance were that some samples were Flow I but not Auer I, or vice versa. These two groups represent 17 (7.7%) and 14 (6.3%), respectively, of the total number of samples, and had frequencies of distant metastasis similar to those of the other high-risk groups, namely, 7/17 and 5/14, respectively. In a multivariate analysis, flow cytometric S-phase value was a stronger prognostic factor than either the Flow and Auer classification. We conclude that when routine FCM DNA analysis is used, diploid or near-diploid samples with a low S-phase value should be reanalyzed with ICM.
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| 38. |
- Borg, Åke, et al.
(author)
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ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer
- 1994
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In: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 81:2, s. 137-144
-
Journal article (peer-reviewed)abstract
- Amplification and overexpression of the ERBB2 (HER-2/neu) oncogene has been implicated as contributing to the development of human breast cancer, and as a predictor of poor survival. In the present non-randomized study of 871 primary invasive breast tumours, ERBB2 activation was significantly correlated to a shorter disease-free and overall survival in the subgroup of patients receiving adjuvant tamoxifen therapy, but not in the untreated group. Further subcategorization demonstrated the relationship to poor prognosis to be confined to lymph node positive and steroid receptor-positive tumours. We suggest that steroid receptor and ERBB2-positive breast tumours are resistant to tamoxifen therapy and, supported by experimental evidence showing an oestrogen receptor dependent up-regulation of ERBB2 expression upon tamoxifen administration, possibly even growth stimulated by the drug.
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| 39. |
- Ewers, Sven-Börje, et al.
(author)
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Prognostic potential of flow cytometric S-phase and ploidy prospectively determined in primary breast carcinomas
- 1992
-
In: Breast Cancer Research and Treatment. - 1573-7217. ; 20:2, s. 93-108
-
Journal article (peer-reviewed)abstract
- In a prospective study of a consecutive breast cancer series accumulated in the period 1978-82, the S-phase fraction (SPF) and ploidy status were determined by flow cytometry performed on cell nuclei derived from samples of 580 primary tumors. Sixty percent of the tumors were non-diploid. After correction for debris the median SPF values were 7.3% overall, 12% for non-diploid tumors, and 2.9% for diploid tumors (2.6% when nodal subsets N2 and N3 and cases with metastases at presentation were excluded). The SPF values correlated both to tumor size (p = 0.008) and to the number of positive axillary lymph nodes (p = 0.03). At clinical follow-up in 1986, 467 unilateral breast cancer patients who had undergone radical treatment for cure could be evaluated with respect to the prognostic value of both the SPF value and ploidy status. The median duration of follow-up was then 59 months (range 2-90), and the median time-to-recurrence 24 months (range 2-69, n = 137). At follow-up in 1991, 201/467 of the patients had died, the median duration of follow-up being 50 months (range 2-126) for the decreased, and 119 (range 6-148) for the survivors. In multivariate analysis (Cox's proportional hazards models), the strongest independent predictors of distant recurrence-free survival (DRFS) were the number of positive axillary lymph nodes (p less than 0.0001), the debris-corrected SPF value alone (p = 0.003, versus p = 0.05 for uncorrected value), and ploidy status combined with the corrected SPF value (p = 0.0002). When age was taken into account, both the corrected SPF value and the ploidy-SPF combination were predictors of crude survival (p = 0.006 and p = 0.002, respectively). In univariate life-table analysis, the 5-year DRFS rate was 93% in node-negative (N0) cases with an SPF less than 7.3%, as compared to 80% in those with an SPF greater than or equal to 7.3% (p = 0.005). Among node-positive cases, the prognostic value of the SPF was confined to those with 1-3 positive nodes, the 5-year DRFS rate being 68% in cases with an SPF less than 7.3%, as compared to 40% in cases with an SPF greater than or equal to 7.3% (p = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
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| 40. |
- Fernö, M., et al.
(author)
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Estrogen and progesterone receptor analyses in more than 4000 human breast cancer samples : A study with special reference to age at diagnosis and stability of analyses
- 1990
-
In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 29:2, s. 129-135
-
Journal article (peer-reviewed)abstract
- Estrogen (ER) and progesterone receptors (PgR) were measured in the same laboratory in more than 4000 breast cancer biopsy samples obtained from 15 different hospitals during ten years. ER was measured with isoelectric focusing and PgR with the dextran-coated charcoal method and Scatchard analysis. The distribution pattern for both ER and PgR was during this time period and for the different hospitals rather similar indicating a good stability of the analytical methods. ER concentration was positively correlated with patient age, with a higher percentage of positive samples and higher concentrations in patients ≥50 years of age compared with patients <50 years. PgR concentration increased with age for patients under 50 years, but a considerable reduction of PgR concentration and of the proportion of positive samples was seen in patients between 50 and 59 years of age. Above this age the PgR concentration again increased with increasing age. The PgR/ER ratio and the proportion of ER- PgR+ samples were higher in patients under 50 years compared to older patients. ER and PgR values decreased during tamoxifen treatment, during pregnancy and after preoperative radiotherapy. Wet weight, DNA and protein were compared as reference parameters for the expression of ER and PgR concentrations. Strong correlations were obtained suggesting that similar information can be obtained with either of these reference parameters.
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