| 51. |
- Jögi, Annika, et al.
(author)
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Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype.
- 2002
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 99:10, s. 7021-7026
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Journal article (peer-reviewed)abstract
- Insufficient oxygen and nutrient supply often restrain solid tumor growth, and the hypoxia-inducible factors (HIF) 1 alpha and HIF-2 alpha are key transcription regulators of phenotypic adaptation to low oxygen levels. Moreover, mouse gene disruption studies have implicated HIF-2 alpha in embryonic regulation of tyrosine hydroxylase, a hallmark gene of the sympathetic nervous system. Neuroblastoma tumors originate from immature sympathetic cells, and therefore we investigated the effect of hypoxia on the differentiation status of human neuroblastoma cells. Hypoxia stabilized HIF-1 alpha and HIF-2 alpha proteins and activated the expression of known hypoxia-induced genes, such as vascular endothelial growth factor and tyrosine hydroxylase. These changes in gene expression also occurred in hypoxic regions of experimental neuroblastoma xenografts grown in mice. In contrast, hypoxia decreased the expression of several neuronal/neuroendocrine marker genes but induced genes expressed in neural crest sympathetic progenitors, for instance c-kit and Notch-1. Thus, hypoxia apparently causes dedifferentiation both in vitro and in vivo. These findings suggest a novel mechanism for selection of highly malignant tumor cells with stem-cell characteristics.
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| 52. |
- Kinhult, Sara, et al.
(author)
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Endothelial damage after treatment with low-molecular weight heparins - a morphological study
- 2003
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In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 37:1, s. 30-33
-
Journal article (peer-reviewed)abstract
- Objective-Recent studies failed to show long-term benefit with low-molecular weight heparins (LMWH) in unstable coronary heart disease. A previous study of vascular effects of the cytostatic agent 5-fluorouracil (5-FU) showed that dalteparin prevented thrombosis induced by 5-FU but endothelial damage was not ameliorated and was present also in animals treated with dalteparin only. This study investigates the influence of LMWH currently in clinical use on arterial endothelium in vivo. Design-Eighty rabbits in four groups were treated with dalteparin, enoxaparin, tinzaparin and saline, respectively. Arterial endothelium was examined after 3, 14, 30 and 60 days with scanning electron microscopy. Results-All three groups treated with LMWH showed moderate damage to the endothelium, with contracted vessel wall and endothelial cells, cell membrane damage, denudation of subendothelium and adhering platelets. Contrarily, the control group exhibited a normal endothelium. Conclusion-Morphologic examination of arterial endothelium shows that all investigated LMWH exert a moderate toxic effect on endothelial cells. The clinical impact of these observations, e. g. concerning effect of long-term LMWH treatment, needs to be further elucidated.
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| 53. |
- Kölby, Lars, 1963, et al.
(author)
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Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters.
- 2003
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In: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1383-8
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Journal article (peer-reviewed)abstract
- The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of (123)I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated (123)I after i.v. injection of (123)I-MIBG. A high concentration of (123)I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n=4 and pheochromocytomas, n=4), reserpine significantly reduced the uptake of (123)I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of (123)I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of (123)I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.
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| 54. |
- Lampic, Claudia, et al.
(author)
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Short- and long-term anxiety and depression in women recalled after breast cancer screening
- 2001
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 37:4, s. 463-469
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Journal article (peer-reviewed)abstract
- The aim was to investigate the psychological consequences of further investigation after breast cancer screening. Study participants include 509 women (61%) recalled due to suspicious findings on screening mammograms, and a matched control group of 285 women (68%) with normal mammograms. Psychological distress was prospectively assessed with the Hospital Anxiety and Depression Scale (HADS). 46% of the women reported borderline or clinically significant anxiety prior to the recall visit. A few days after the visit, anxiety and depression had decreased significantly (P<0.01) in women informed about normal or benign results at the recall clinic, while reported distress remained at relatively high levels in women referred to surgical biopsy. The results demonstrate the adverse short-term effect of a delay in receiving false-positive results, but do not indicate that the recall experience results in long-term anxiety or depression for a majority of women.
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| 55. |
- Malmström, Per, et al.
(author)
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Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.
- 2003
-
In: European journal of cancer (Oxford, England : 1990). - 0959-8049. ; 39, s. 1690-
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Journal article (peer-reviewed)abstract
- The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.
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| 56. |
- Mertens, Fredrik, et al.
(author)
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Radiation-associated sarcomas are characterized by complex karyotypes with frequent rearrangements of chromosome arm 3p
- 2000
-
In: Cancer Genetics and Cytogenetics. - 0165-4608. ; 116:2, s. 89-96
-
Journal article (peer-reviewed)abstract
- Ionizing radiation is a well-known risk factor for sarcoma development. To investigate whether radiation-associated sarcomas are characterized by chromosome aberrations that distinguish them from de novo sarcomas, we identified those patients in our series of more than 500 cytogenetically abnormal sarcomas that fulfilled the following criteria: (1) each patient should have been irradiated for another malignancy at least 3 years prior to the sarcoma diagnosis, and (2) the sarcoma should have developed within the field of radiation. Ten patients fulfilling these criteria could be retrieved (median age at sarcoma diagnosis was 55 years, range 17-79; median latency period between primary tumor and radiation-associated sarcoma was 9 years, range 4-30). The diagnoses were typical for radiation-associated sarcomas: 2 each of malignant fibrous histiocytoma, leiomyosarcoma, and pleomorphic sarcoma, and 1 each of osteosarcoma, fibrosarcoma, myxofibrosarcoma, and spindle cell sarcoma. All 10 cases had relatively complex karyotypes with multiple, mostly unbalanced, structural rearrangements, similar to what has been reported in de novo sarcomas of the corresponding histologic subtypes. The only cytogenetic features that were unusually frequent among the radiation-associated sarcomas were the finding of unrelated clones in 3 cases, and loss of material from chromosome arm 3p, in particular 3p21-3pter, in 8 cases. Loss of the same chromosome segment has been described in 4 of the 8 previously published cases of radiation-associated sarcomas that have been analyzed after short-term culturing, which makes this imbalance significantly (P < 0.001) more frequent among radiation-associated sarcomas (12 of 18 cases) than among unselected cases of the corresponding histologic subtypes (74 of 282 cases). In contrast to the cytogenetic results, no 3p deletions were detected among the 6 cases of the present series that could be analyzed by comparative genomic hybridization (CGH). The most frequent imbalance detected by CGH was gain of 15cen-q15 (3 cases), followed by loss of chromosome 13 and gain of 5p, and 7cen-q22, each detected in 2 cases.
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| 57. |
- Mogren, Ingrid, et al.
(author)
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Reproductive factors have low impact on the risk of different primary brain tumours in offspring
- 2003
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In: Neuroepidemiology. - : S. Karger. - 0251-5350 .- 1423-0208. ; 22:4, s. 249-254
-
Journal article (peer-reviewed)abstract
- Objectives: The aim of our study was to investigate whether reproductive factors influence the risk of primary brain tumours (PBT) in offspring. Methods: Data on all deliveries in two Swedish counties from 1955 to 1990 were extracted from two birth registries. The follow-up period closed at the end of 1994, with subjects followed up to early middle age. Incidence rates of malignancy for 1958-1994 were obtained from the Swedish Cancer Registry. Standardised incidence ratios (SIR) and relative risks were calculated for astrocytomas, primitive neuroectodermal tumour, ependymoma and meningiomas in offspring. Results: Few associations were detected. High birth weight indicated an increased risk for astrocytomas grade I and II for all primary brain tumours, and the risk was close to significance for astrocytomas grade I-II (SIR = 3.64; CI = 0.98-9.31). For children under 15 years of age the risk for astrocytomas grade I and II was further increased (SIR = 4.44; Cl = 1.19-11.38). Conclusions:A consistent pattern of non-association indicated a low impact of intrauterine environment on the future development of primary brain tumours in offspring up to early middle age.
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| 58. |
- Möller, Torgil, et al.
(author)
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Survival of children with liver tumours in Europe 1978--1989
- 2001
-
In: European Journal of Cancer. - 1879-0852. ; 37:6, s. 744-749
-
Journal article (peer-reviewed)abstract
- Hepatic tumours are rare in childhood. Within the frame of the EUROCARE II study, a total of 328 liver tumours in patients aged 0--14 years were reported during the period 1978--1989. The childhood cancer registries in UK and Germany contributed approximately a third of the cases each. Hepatoblastoma accounted for 71% of cases. The 5-year survival was 36% 95% confidence interval (CI) 28--46%, with no significant difference between the genders. Patients aged 10--14 years did worse, especially boys. Survival improved significantly during the study period. Survival in hepatocellular carcinoma was lower, 20% (95% CI 6--52%), and showed no improvement during the study period.
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| 59. |
- Naumburg, Estelle, et al.
(author)
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Perinatal exposure to infection and risk of childhood leukemia
- 2002
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In: Medical and Pediatric Oncology. - : Wiley. - 0098-1532 .- 1096-911X. ; 38, s. 391-
-
Journal article (peer-reviewed)abstract
- BACKGROUND: A population-based case-control study was conducted to investigate the association between childhood leukemia and infectious exposures during pregnancy and early neonatal period.PROCEDURE: Children born and diagnosed with leukemia between 1973 and 1989 in Sweden (578 lymphatic, 74 myeloid) were selected as cases. One control was randomly selected for each case and individually matched by sex, month, and year of birth. Children with Down's syndrome were excluded. Exposure data were blindly abstracted from antenatal, obstetric, and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression.RESULTS: A history of maternal infection was not significantly associated with childhood leukemia, OR = 1.25 (95% CI 0.95-1.65). Maternal lower genital tract infection significantly increased the risk of childhood leukemia, OR = 1.78 (95% CI 1.17-2.72), and especially for children over 4 years of age at diagnosis, OR = 2.01 (95% CI 1.12-3.80). Neonatal infection was not associated with the risk of leukemia. The results remained unaltered after adjustment for potential confounders, and separate analyses for myeloid and lymphoid leukemia.CONCLUSIONS: We could document an association between exposure to maternal lower genital tract infection in utero, and a subsequent risk for childhood leukemia, which indicate the importance of an early exposure.
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| 60. |
- Persson, Kristin, et al.
(author)
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Severe lung lesions caused by Salmonella are prevented by inhibition of the contact system
- 2000
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 192:10, s. 1415-1424
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Journal article (peer-reviewed)abstract
- Vascular damage induced by trauma, inflammation, or infection results in an alteration of the endothelium from a nonactivated to a procoagulant, vasoconstrictive, and proinflammatory state, and can lead to life-threatening complications. Here we report that activation of the contact system by Salmonella leads to massive infiltration of red blood cells and fibrin deposition in the lungs of infected rats. These pulmonary lesions were prevented when the infected animals were treated with H-D-Pro-Phe-Arg-chloromethylketone, an inhibitor of coagulation factor XII and plasma kallikrein, suggesting that inhibition of contact system activation could be used therapeutically in severe infectious disease.
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