| 1. |
- Abel, Frida, 1974, et al.
(författare)
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Gain of chromosome arm 17q is associated with unfavourable prognosis in neuroblastoma, but does not involve mutations in the somatostatin receptor 2(SSTR2) gene at 17q24.
- 1999
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 81:8, s. 1402-9
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Tidskriftsartikel (refereegranskat)abstract
- Deletion of chromosome arm 1p and amplification of the MYCN oncogene are well-recognized genetic alterations in neuroblastoma cells. Recently, another alteration has been reported; gain of the distal part of chromosome arm 17q. In this study 48 neuroblastoma tumours were successfully analysed for 17q status in relation to known genetic alterations. Chromosome 17 status was detected by fluorescence in situ hybridization (FISH). Thirty-one of the 48 neuroblastomas (65%) showed 17q gain, and this was significantly associated with poor prognosis. As previously reported, 17q gain was significantly associated with metastatic stage 4 neuroblastoma and more frequently detected than both deletion of chromosome arm 1p and MYCN amplification in tumours of all stages. 17q gain also showed a strong correlation to survival probability (P = 0.0009). However, the most significant correlation between 17q gain and survival probability was observed in children with low-stage tumours (stage 1, 2, 3 and 4S), with a survival probability of 100% at 5 years from diagnosis for children with tumours showing no 17q gain compared to 52.5% for those showing 17q gain (P = 0.0021). This suggests that 17q gain as a prognostic factor plays a more crucial role in low-stage tumours. Expression of the somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, has in previous studies been shown to be positively related to survival in neuroblastoma. A point mutation in the SSTR2 gene has earlier been reported in a human small-cell lung cancer. In this study, mutation screening of the SSTR2 gene in 43 neuroblastoma tumours was carried out with polymerase chain reaction-based single-stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing, and none of the tumours showed any aberrations in the SSTR2 gene. These data suggest that mutations in the SSTR2 gene are uncommon in neuroblastoma tumours and do not correlate with either the 17q gain often seen or the reason some tumours do not express SSTR2 receptors. Overall, this study indicates that gain of chromosome arm 17q is the most frequently occurring genetic alteration, and that it is associated with established prognostic factors.
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| 2. |
- Ejeskär, K, et al.
(författare)
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Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT gene.
- 1998
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 77:11, s. 1787-91
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a heterogeneous childhood tumour of the sympathetic nervous system, in which deletions of chromosomal region 1p and amplification of the MYCN oncogene correlate with aggressive tumour behaviour. However, the majority of neuroblastoma tumours show neither of these aberrations, indicating that other chromosomal regions may be involved in tumorigenesis. Here, we report findings of loss of heterozygosity (LOH) on chromosome 3. In our neuroblastoma material, nine of 59 (15.3%) tested tumours showed allelic loss of chromosome 3p markers. We found significant clinical and biological differences between tumours with the loss of one entire chromosome 3 vs tumours with partial loss in chromosome region 3p. All children with tumours with whole chromosome 3 loss are long-term survivors, whereas all children with tumours showing partial 3p LOH have died from tumour progression. A consensus region found to be deleted in all the tumours with 3p deletions was defined by markers D3S1286 and D3S1295, i.e. 3p25.3-p14.3, distal to the FHIT gene.
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| 3. |
- Johanson, V, et al.
(författare)
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Comparison of survival between malignant neuroendocrine tumours of midgut and pancreatic origin.
- 1999
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 80:8, s. 1259-61
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Tidskriftsartikel (refereegranskat)abstract
- The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated.
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| 4. |
- Sundfeldt, Karin, 1962, et al.
(författare)
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The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPbeta during epithelial tumour progression.
- 1999
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 79:7-8, s. 1240-8
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Tidskriftsartikel (refereegranskat)abstract
- The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPalpha, -beta, -delta and -zeta in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPalpha and C/EBPbeta were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPbeta was located in the nuclei of the cells, in contrast to C/EBPalpha, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPbeta indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPalpha. C/EBPdelta and -zeta demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPdelta and -zeta. Western blotting demonstrated that C/EBPalpha, -beta, -delta and -zeta were present in a majority of the samples. The amount of C/EBPbeta increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPbeta as a potential marker for these tumours. As C/EBPbeta is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression.
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| 5. |
- Tisell, Lars-Eric, 1931, et al.
(författare)
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Expression of somatostatin receptors in oncocytic (Hürthle cell) neoplasia of the thyroid.
- 1999
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 79:9-10, s. 1579-82
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Tidskriftsartikel (refereegranskat)abstract
- Ten consecutive patients with Hürthle cell lesions of the thyroid (nodule/adenoma/carcinoma) were studied by (111)In-DTPA-D-Phe1-octreotide scintigraphy. Octreotide scintigraphy localized the primary Hürthle cell tumour in eight patients as distinct areas of increased uptake of radionuclide. Two patients with Hürthle cell carcinoma, previously thyroidectomized, had their metastases visualized by octreotide scintigraphy. Northern analyses showed expression of multiple somatostain receptor subtypes. Visualization of the Hürthle cell tumour may be due to a higher expression of somatostatin receptors in the lesions than in surrounding normal thyroid tissue. The tissue/blood (111)In concentration ratios for tumour samples from five patients showed clearly higher values than observed for normal connective tissue, muscle or lymph nodes. A relatively high uptake of (111)In was also observed in goiter tissue, which may lead to misinterpretations. The main indication for octreotide scintigraphy in patients with Hürthle cell carcinoma is suspicion of metastatic disease.
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| 6. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The in vitro radiosensitivity of human head and neck cancers
- 1998
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Ingår i: Br J Cancer. - 0007-0920. ; 77:12, s. 2371-5
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Tidskriftsartikel (refereegranskat)abstract
- A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical specimens of malignant head and neck tumours of different histologies. Using a soft-agar clonogenic assay, the material was assessed for the ability to grow in culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74% (104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2 was obtained for 88 of 140 specimens, representing a success rate of 63% with a mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no significant differences in radiosensitivity between different sites of the head and neck region. There were no significant relationships between SF2 and disease stage, nodal status, tumour grade, patient age, primary tumour growth pattern and CFE. The results were compared with those for other tumour types previously analysed with the same assay. The distribution of the SF2 values for the head and neck tumours was similar to that for 145 cervix carcinomas and there was no significant difference in mean radiosensitivity between the two tumour types. Also, there was no significant difference in radiosensitivity between head and neck tumours and either breast or colorectal cancers. However, a group of eight lymphomas was significantly more radiosensitive. These results confirm the feasibility of carrying out radiosensitivity measurements using a soft-agar clonogenic assay on head and neck tumours. In addition, the work has shown that radiosensitivity is independent of many clinical parameters and that the mean value is similar to that reported for cervix carcinomas.
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| 7. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The lack of correlation between proliferation (Ki-67, PCNA, LI, Tpot), p53 expression and radiosensitivity for head and neck cancers
- 1999
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Ingår i: Br J Cancer. - 0007-0920. ; 80:9, s. 1400-4
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Tidskriftsartikel (refereegranskat)abstract
- A study was made of the relationship between measurements of radiosensitivity versus proliferation and p53 status in head and neck cancers. Inherent tumour radiosensitivity was assessed as surviving fraction at 2 Gy (SF2) using a clonogenic soft agar assay (n = 77). The results were compared to data on proliferation obtained by both flow cytometry (labelling index (LI), the potential doubling time (Tpot) n = 55) and immunohistochemistry (Ki-67 and PCNA; n = 68), together with immunohistochemical p53 expression (n = 68). There were no overall significant differences in the median values of the various parameters analysed for the different sites within the head and neck region, disease stages, grades of tumour differentiation or nodal states. A subgroup analysis showed that oropharyngeal (n = 22) versus oral cavity (n = 35) tumours were more radiosensitive (P = 0.056) and had a higher Ki-67 index (P = 0.001). Node-positive tumours had higher LI (P = 0.021) and a trend towards lower Tpot (P = 0.067) values than node-negative ones. No correlations were seen between SF2 and any of the parameters studied. The long-standing dogma of an increased radiosensitivity of rapidly proliferating cells in contrast to slowly proliferating cells was not confirmed. The study shows that parallel measurements of different biological markers can be obtained for a large number of patients with head and neck cancers. The independence of the various parameters studied suggests that there may be potential for their combined use as prognostic factors for the outcome of radiotherapy.
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| 8. |
- Nilsson, Ola, 1957, et al.
(författare)
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Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.
- 1998
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Ingår i: British journal of cancer. - 0007-0920. ; 77:4, s. 632-7
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Tidskriftsartikel (refereegranskat)abstract
- We have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [111In]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The 111In activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 111In activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction). Incubation of midgut carcinoid tumours in primary culture with octreotide (10 microM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.
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| 9. |
- Wängberg, Bo, 1953, et al.
(författare)
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Accumulation of natural killer cells after hepatic artery embolisation in the midgut carcinoid syndrome.
- 1995
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Ingår i: British journal of cancer. - 0007-0920. ; 71:3, s. 617-8
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Tidskriftsartikel (refereegranskat)abstract
- Eleven patients with disseminated midgut carcinoid tumour disease were subjected to hepatic artery embolisation. In six patients, lymphocytosis with a predominance of NK cells occurred and the cytotoxic activity of isolated lymphocytes increased. A relation between NK cell accumulation and subsequent radiological and biochemical response was observed, and it is suggested that anti-tumour mechanisms other than ischaemia may contribute to the therapeutic response in these patients.
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| 10. |
- Wängberg, Bo, 1953, et al.
(författare)
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Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.
- 1996
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Ingår i: British journal of cancer. - 0007-0920. ; 73:6, s. 770-5
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Tidskriftsartikel (refereegranskat)abstract
- After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors.
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