| 1. |
- Adami, Johanna, et al.
(författare)
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Cancer risk following organ transplantation : a nationwide cohort study in Sweden
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1221-1227
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Tidskriftsartikel (refereegranskat)abstract
- A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970-1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7-4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8-63.2), lip cancer (SIR 53.3; 95% CI 38.0-72.5) and of non-Hodgkin's lymphoma (NHL) (SIR 6.0; 95% CI 4.4-8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3-16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two- to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.
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| 2. |
- Bernsen, MR, et al.
(författare)
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On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 88:3, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- A large number of studies have indicated that specific immune reactivity plays a crucial role in the control of malignant melanoma. In this context, expression of MHC I, MHC II and B7 molecules by melanoma cells is seen as relevant for the immune response against the tumour. For a better understanding of the biological relevance of MHC II and B7 expression by tumour cells in metastatic melanoma, we studied the expression of these molecules in melanoma metastases in relation to the inflammatory response, regression of the tumour and survival from 27 patients treated with biochemotherapy (30 mg m-2 Cisplatin and 250 mg m-2 decarbazine (dimethyl-triazene-imidazole-carboxamide, DTIC) on days 1-3 i.v., and 107 IU IFN-a2b 3 days a week s.c., q. 28d). In 19 out of 27 lesions studied, we found expression of MHC II by the tumour cells, while only in one out of II tumour biopsies obtained from untreated metastatic melanoma patients, MHC II expression was detected. Expression of B7.1 and B7.2 by tumour cells was found in nine out of 24 and 19 out of 24 lesions, respectively. In all cases where B7.1 expression was found, expression of B7.2 by the tumour cells was also seen. In general, no or only few inflammatory cells positive for B7 were found. Expression of MHC II by tumour cells was positively correlated with the presence of tumour-infiltrating lymphocytes, regression of the lesion, and with time to progression (TTP) and overall survival (OS) of the patient. However, no significant correlation between B7.1 or B7.2 expression and regression of the tumour, TTP or OS was found. In light of other recent findings, these data altogether do support a role as biomarker for MHC II expression by tumour cells, however, its exact immunological pathomechanism(s) remain to be established. ⌐ 2003 Cancer Research UK.
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| 3. |
- Birringer, M, et al.
(författare)
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Vitamin E analogues as inducers of apoptosis : Structure-function relation
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 88:12, s. 1948-1955
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Tidskriftsartikel (refereegranskat)abstract
- Recent results show that a-tocopheryl succinate (a-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of a-TOS with lower number of methyl substitutions on the aromatic ring were less active than a-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on a-TOS and d-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. a-tocotrienol (a-T3 H) failed to induce apoptosis, while ?-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of ?-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.
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| 4. |
- Bümming, Per, 1965, et al.
(författare)
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Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:3, s. 460-4
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Tidskriftsartikel (refereegranskat)abstract
- Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings - palliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.
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| 5. |
- Dabrosin, Charlotta, 1961-, et al.
(författare)
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Oestradiol enhances tumour regression induced by B7-I/IL-2 adenoviral gene transfer in a murine model of breast cancer
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:2, s. 385-390
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Tidskriftsartikel (refereegranskat)abstract
- The majority of breast cancers are oestrogen dependent and although current treatment strategies have improved, approximately 50% of the patients will develop metastasis. New treatments that result in long-term systemic immunity are therefore being developed. We have previously shown that adenoviral gene transfer of B7-I/IL-2 to murine breast cancer induces a high rate of complete turnout regression and systemic immunity. Since oestrogens not only affect breast cancer but also have been shown to modulate immune function and secretion of immune-regulatory cytokines, we explored whether administration of oestradiol altered the immune response induced by an adenoviral vector expressing B7-I/IL-2. An oestrogen-dependent murine breast cancer tumour was used in ovariectomised mice, supplemented either oestradiol or placebo. We report the somewhat unexpected finding that intratumoral injection of adenovirus expressing B7-I/IL-2 induces complete turnout regression in 76% of oestradiol-supplemented mice, while only 18% of the tumours regressed in the oestrogen-depleted group. Cured mice in both groups exhibited a similar CTL response against the tumour antigen. However, intratumoral IFN-? levels, 2 days after B7-I/IL-2 injection, were significantly higher in mice treated with oestradiol compared to placebo. This may be one mechanism explaining the higher response rate of tumours in oestradiol-replenished mice.
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| 6. |
- Dalen, Helge, et al.
(författare)
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a-tocopheryl succinate sensitises a T lymphoma cell line to TRAIL-induced apoptosis by suppressing NF-?B activation
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 88:1, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Activation of nuclear factor-?B (NF-?B) can interfere with induction of apoptosis triggered by the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L). Therefore, agents that suppress NF-?B activation may sensitise cells to TRAIL-dependent apoptosis. Exposure of Jurkat cells to TRAIL resulted in massive and saturable apoptosis induction, following an initial lag time. This lag was abolished by pretreatment of the cells with subapoptotic doses of a-tocopheryl succinate (a-TOS) or the proteasome inhibitor MGI32. Exposure of the cells to TRAIL led to a rapid, transient activation of NF-?B, a process that was suppressed by cell pretreatment with a-TOS or MGI32. Activation of NF-?B by TNF-a prior to TRAIL exposure increased resistance of the cells to TRAIL-mediated apoptosis. We conclude that a-TOS sensitises cells to TRAIL killing, at least in some cases, through inhibition of NF-?B activation. This further supports the possibility that this semisynthetic analogue of vitamin E is a potential adjuvant in cancer treatment, such as in the case of TRAIL-mediated inhibition of cancer.
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| 7. |
- Dryver, ET, et al.
(författare)
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Follow-up of patients with Hodgkin's disease following curative treatment: the routine CT scan is of little value
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 89:3, s. 482-486
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Tidskriftsartikel (refereegranskat)abstract
- A total of 10-40% of patients with Hodgkin's disease relapse following initial curative therapy. Intensive follow-up is resource intensive and may identify false relapses. We performed a retrospective review of all patients with Hodgkin's disease treated at our centre between 1990 and 1999 to evaluate the utility of the components of follow-up. A total of 107 patients met the inclusion and exclusion criteria. The median age was 33 years and the median duration of follow-up 38 months. The total number of follow-up visits was 1209 and total number of CT scans 283. There were 109 suspected relapses of which 22 proved to be true relapses. Of the latter, 14 were identified clinically, six radiologically and two via lab testing. The routine CT scan detected only two relapses (9%), yet accounted for 29% of the total follow-up costs. Based on data from our centre, the cost per true relapse was $6000 US, 49% incurred by radiological tests. The majority of the cost of follow-up was incurred by routine follow-up (84%) as opposed to the investigation of suspected relapses (16%). We conclude that most true relapses are clinically symptomatic and that the routine CT is an expensive and inefficient mode of routine follow-up.
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| 8. |
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| 9. |
- Erba, E, et al.
(författare)
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Effect of Aplidin in acute lymphoblastic leukaemia cells.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:4, s. 763-73
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Tidskriftsartikel (refereegranskat)abstract
- The cytotoxic effect of Aplidin was investigated on fresh leukaemia cells derived from children with B-cell-precursor (BCP) acute lymphoblastic leukaemia (ALL) by using stromal-layer culture system and on four cell lines, ALL-PO, Reh, ALL/MIK and TOM-1, derived from patients with ALL with different molecular genetic abnormalities. In ALL cell lines Aplidin was cytotoxic at nanomolar concentrations. In the ALL cell lines the drug-induced cell death was clearly related to the induction of apoptosis and appeared to be p53-independent. Only in ALL-PO 20 nM Aplidin treatment caused a block of vascular endothelial growth factor (VEGF) secretion and downregulation of VEGF-mRNA, but Aplidin cytotoxicity does not seem to be related to VEGF inhibition since the sensitivity of ALL-PO cells to Aplidin is comparable to that observed for the other cells used. Aplidin induced a G(1) and a G(2) M block in ALL cell lines. In patient-derived leukaemia cells, Aplidin induced a strong cytotoxicity evidenced in a stroma-supported immunocytometric assay. Cells from children with genetic abnormalities such as t(9;22) and t(4;11) translocations, associated with an inferior treatment outcome, were sensitive to Aplidin to the same extent as that observed in other BCP-ALL cases. Aplidin exerted a strong cell killing effect (>88%) against primary culture cells from five relapsed ALL cases, at concentrations much lower than those reported to be achieved in plasma of patients receiving Aplidin at recommended doses. Taken together these data suggest that Aplidin could be a new anticancer drug to be investigated in ALL patients resistant to available therapy.
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| 10. |
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