| 31. |
- Franklin, Gary C., et al.
(författare)
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An Inr-containing sequence flanking the TATA box of the human c-sis (PDGF-B) proto-oncogene promoter functions in cis as a co-activator for its intronic enhancer
- 1995
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Ingår i: Oncogene. - 0950-9232 .- 1476-5594. ; 11:9, s. 1873-1884
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- High-level activity of the human PDGF-B promoter in choriocarcinoma cell lines depends upon an atypical, intronic enhancer-like element which does not function with heterologous promoters tested. An extensive series of mutant PDGF-B promoter-driven constructs identified a sequence flanking the TATA box which is required specifically for enhancer-mediated transcription in human choriocarcinoma cell lines. This element, which we here term an enhancer-dependent cis co-activator (EDC) contains an Inr (initiator) consensus sequence upstream of the TATA box which is required, but not sufficient for its function. Requirement for the EDC is cell type-specific, since it was dispensable for enhancer-mediated transcription in a human breast cancer cell line. Although it lies within the region defined, the TATA box itself is not required for EDC function, or for basal promoter function which may derive from a second Inr-like sequence situated at the transcriptional start site. These observations indicate that interactions between some promoter and enhancer elements may be more complex than that generally described for 'classical' enhancer systems and may suggest an additional function for the initiator motif.
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| 32. |
- Frängsmyr, Lars, et al.
(författare)
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Cell- and region-specific expression of biliary glycoprotein and its messenger RNA in normal human colonic mucosa
- 1995
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 55:14, s. 2963-2967
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Tidskriftsartikel (refereegranskat)abstract
- The localization of biliary glycoprotein (BGP) and its mRNA in normal colonic mucosa was studied by immunohistochemistry and in situ hybridization. BGP mRNA was confined to columnar epithelial cells and expressed abundantly in the superficial mature cells and at low levels in differentiating cells in the upper crypts. Epithelial expression of BGP coincided with that of BGP mRNA. Ultrastructurally, BGP was localized to microfilaments of the fuzzy coat of the columnar cells at the luminal surface and the upper crypts. Additionally, BGP was found in cryptal caveolated cells. The results are consistent with primary transcriptional regulation of BGP production and suggest that BGP synthesis is controlled by the degree of cytodifferentiation. The fuzzy-coat localization of BGP implies a role in nonspecific defense mechanisms against pathogens.
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| 33. |
- Gudmundsson, Thorkell E, et al.
(författare)
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The prognostic information of DNA ploidy and S-phase fraction may vary with histologic grade in endometrial carcinoma
- 1995
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 34:6, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- DNA ploidy and S-phase fraction (SPF) were determined by flow cytometry on paraffin-embedded tumor material from 243 patients treated during 1980-1985. Patients with well differentiated and moderately differentiated tumors without solid areas (n = 351) formed a low-risk group (corrected 5-year survival 90%). Twenty-four patients, dead of disease within 5 years, were compared with 52 survivors. The estimated death risk was higher for those with SPF > or = 8.0% compared with those with SPF < 8.0% (odds ratio = 18.2; p < 0.001). SPF was the only independent prognostic factor in a multivariate analysis also including age, clinical stage and grade of differentiation. Patients with moderately differentiated tumors with solid areas or poorly differentiated tumors (n = 208) were regarded as a high-risk group. There was a difference in survival according to ploidy; the corrected 5-year survival was 75% for 106 patients with diploid tumors compared with 44% for those with non-diploid tumors (p < 0.0001). In a multivariate analysis DNA ploidy, age and clinical stage were independent prognostic factors, whereas SPF was no longer significant. Thus, DNA ploidy and SPF have different prognostic values depending on histological grade of endometrial carcinoma.
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| 34. |
- Gullberg, U, et al.
(författare)
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Receptors for hematopoietic regulatory cytokines : overview of structure and function
- 1995. - 1
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Ingår i: Cytokines: : Interleukins and Their Receptors - Interleukins and Their Receptors. - Boston, MA : Springer US. - 0927-3042. - 9780792336365 - 9781461312413 ; 80, s. 1-24
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Bokkapitel (refereegranskat)abstract
- The production of blood cells is regulated by the action of external factors, cytokines, that can be released by many cell types. In the first place, a population of multipotent stem cells, mostly in the resting Go phase of the cell cycle, but with self-renewal capacity, gives rise to progenitor cells that are predetermined for differentiation into all kinds of blood cells. Expression of genes for cytokine receptors leads to external regulation of hematopoiesis by cytokines which bind to the receptors, resulting in modifications of proliferation and differentiation, as cytokines are not only growth factors, but are also maturation factors capable of directing hematopoiesis towards functionally competent cells. What is more, they are survival factors capable of suppressing programmed cell death (apoptosis). This is of particular importance for the viability of stem cells which must be preserved. Thus cytokines can act at all positions of the hematopoietic family tree, and the response can differ from proliferation and differentiation of progenitor cells to functional activation of mature cells. Under physiological conditions, during constitutive hematopoiesis, the regulatory cytokines are produced locally, for instance by stromal ceils of the microenvironment, and act locally in a paracrine manner [2].
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| 35. |
- Hardell, L., et al.
(författare)
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Meta-analysis of four Swedish case-control studies on exposure to pesticides as risk-factor for soft-tissue sarcoma including the relation to tumour localization and histopathological type
- 1995
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Ingår i: International Journal of Oncology. - 1019-6439. ; 6:4, s. 847-851
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Tidskriftsartikel (refereegranskat)abstract
- In four previous case-control studies we have shown an association between exposure to phenoxyacetic acids or chlorophenols and soft-tissue sarcoma (STS). These chemicals are contaminated by dioxins and dibenzofurans, some of which are known carcinogens in experimental animals. In a meta-analysis of our four studies we studied such exposure including the relation to tumour localization and histopathological type of STS. In total 434 histopathologically verified STS cases and 948 controls were included. Anatomical tumour localization was assessed by scrutinizing medical records for all cases. In the analysis stratification was made for age, vital status and study. Significantly increased risks were obtained for exposure to phenoxyacetic acids and chlorophenols, odds ratios 2.7 and 3.3, 95% confidence intervals 1.9-4.7 and 1.8-6.1, respectively. The increased risk was independent of histopathological subtype and anatomical site although especially high odds ratios were obtained for body sites close to areas where dermal contact may occur in sprayers. Phenoxyacetic acids and chlorophenols with their contaminating dioxins and dibenzofurans should be regarded as carcinogenic for STS regardless of tumour localization and histopathological type.
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| 36. |
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| 37. |
- Lindblad, Per, 1953-, et al.
(författare)
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International renal-cell cancer study. V. Reproductive factors, gynecologic operations and exogenous hormones
- 1995
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Ingår i: International Journal of Cancer. - Hoboken, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 61:2, s. 192-198
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Tidskriftsartikel (refereegranskat)abstract
- The relationships between reproductive factors, exogenous hormones and renal-cell cancer were examined in an international, multicenter, population-based, case-control study undertaken in 1989-1991. Data from 5 centers situated in Australia, Denmark, Germany, Sweden and the United States included for analysis 608 women with renal-cell cancer and 766 female controls. A significant trend in risk (p = 0.002) was associated with number of births, with an 80% excess risk for 6 or more births [RR = 1.8, 95% confidence interval (CI) = 1.1 to 2.9] compared with one birth. A decreasing risk was seen for increasing age at first birth, although this was confounded by body-mass index and number of births. A suggestive reduction of risk was also seen for increasing age at menarche. Age at menopause was unrelated to risk of renal-cell cancer. An increased risk was observed for women having had both a hysterectomy and an oophorectomy. Use of oral contraceptives in non-smoking women reduced the risk of renal-cell cancer (RR = 0.5, 95% CI = 0.4 to 0.8); this reduction increased with longer duration of use. No association was observed for estrogen replacement therapy. Our results indicate that certain hormonal and reproductive variables may be related to risk of renal-cell cancer and deserve further investigation, both epidemiologically and experimentally.
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| 38. |
- Lindnér, Per, 1956, et al.
(författare)
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Influence of hepatic artery occlusion and desferrioxamine on liver-tumour growth.
- 1995
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Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 63:4, s. 592-6
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms behind tumour regression during ischaemic therapy of liver malignancy are not thoroughly elucidated. Ischaemia-reperfusion injury and release of free radicals is one mechanism suggested. The aim of the present study was to explore whether inhibition of hydroxyl radicals, by complex binding Fe with desferrioxamine (DFO), counteracted the retardation in tumour growth rate after HAL and whether DFO in itself had an effect on tumour growth in 2 experimental rat liver tumours. Rats with a hepatoma or an adenocarcinoma were subjected to HAL or to a sham procedure with or without additional injections of DFO daily for 2 or 7 days. HAL had an inhibitory effect on tumour growth rate. The effect of HAL was not counteracted by DFO, while DFO alone caused a decrease in tumour volume. There was an additive effect of DFO and HAL on tumour growth rate in both tumour systems. In vitro there was a growth inhibitory effect of DFO in both tumours, more pronounced in the hepatoma than in the adenocarcinoma. Our findings indicate that the effect of HAL is not mediated by release of oxygen free radicals. In the adenocarcinoma system, an additive effect of DFO and HAL was seen. As a rate-limiting enzyme for DNA synthesis is dependent on iron, depletion of iron can decrease mitotic activity, a mechanism that could explain the effect of DFO on tumour growth.
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| 39. |
- Mandel, J. S., et al.
(författare)
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International renal-cell cancer study. IV. Occupation
- 1995
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Ingår i: International Journal of Cancer. - New York, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 61:5, s. 601-605
-
Tidskriftsartikel (refereegranskat)abstract
- The relationship between renal-cell cancer (RCC) and occupation was investigated in an international multicenter population-based case-control study. Study centers in Australia, Denmark, Germany, Sweden and the United States interviewed 1732 incident RCC cases and 2309 controls. Significant associations were found with employment in the blast-furnace or the coke-oven industry [relative risk (RR), 1.7; 95% confidence interval (CI), 1.1-2.7], the iron and steel industry (RR, 1.6; 95% CI, 1.2-2.2) and exposure to asbestos (RR, 1.4; 95% CI, 1.1-1.8), cadmium (RR, 2.0; 95% CI, 1.0-3.9), dry-cleaning solvents (RR, 1.4; 95% CI, 1.1-1.7), gasoline (RR, 1.6; 95% CI, 1.2-2.0) and other petroleum products (RR, 1.6; 95% CI, 1.3-2.1). Asbestos, petroleum products and dry-cleaning solvents appear to merit further investigation, in view of the relationship between risk and duration of employment or exposure and after adjustment for confounding. There was a negative association between RCC and education, but it was not consistent across all centers. Overall, the results of our multicenter case-control study suggest that occupation may be more important in the etiology of RCC than indicated by earlier studies.
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| 40. |
- McCredie, M., et al.
(författare)
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International renal-cell cancer study. II. Analgesics
- 1995
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Ingår i: International Journal of Cancer. - New York, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 60:3, s. 345-349
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Tidskriftsartikel (refereegranskat)abstract
- There has been concern about the role of analgesics in the development of renal-cell cancer, although a few studies have reported moderately elevated risks with regular or long-term use. In a large international case-control study of renal-cell cancer we examined, among other hypotheses, the effect of phenacetin-containing and of other types of analgesics: paracetamol (acetaminophen), salicylates (mainly aspirin) and pyrazolones (e.g., antipyrine or phenazone). Relative risks, adjusted for the effects of age, sex, body-mass index, tobacco smoking and study centre, were not significantly increased with intake of phenacetin, either when lifetime consumption was categorized at the level of > or = 0.1 kg or when subjects were subdivided further by amount. Nor were paracetamol, salicylates or pyrazolones linked with renal-cell cancer. No consistently increasing risks with consumption level was found. The lack of association was not altered by restricting analgesic use to that which occurred 5 or 10 years before the defined "cut-off" date or when analysis was restricted to exclusive users of a particular type of analgesic. Neither was the risk influenced by the rate of consumption or whether the consumption had occurred at a young age. Our study provides clear evidence that aspirin is unrelated to renal-cell cancer risk, and our findings do not support the hypothesis that analgesics containing phenacetin or paracetamol increase the risk, although the number of "regular" users and the amount of these types of analgesic consumed were too small to confidently rule out a minor carcinogenic effect of phenacetin and paracetamol.
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