| 31. |
- Ahlin, Cecilia, et al.
(author)
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Aberrant expression of cyclin E in low-risk node negative breast cancer
- 2008
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:8, s. 1539-1545
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Journal article (peer-reviewed)abstract
- Background. Cyclin E is a cell cycle regulatory protein which occurs in G1, peaks in late G1 and is degraded in early S-phase. Cyclin E overexpression appears to be an independent prognostic factor for overall survival in breast cancer. Material and Methods. Nuclear cyclin A is a reliable marker for S-and G2-phases. Consequently, aberrant expression of cyclin E can be detected by simultaneous immunostainings for cyclin A and cyclin E. Studies have shown that aberrant cyclin E might provide additional prognostic information compared to that of cyclin E alone. This study aimed to investigate cyclin E and aberrant cyclin E expression in low-risk node negative breast cancer. We compared women that died from their breast cancer (n=17) with women free from relapse>8 years after initial diagnosis (n=24). All women had stage I, low risk breast cancer. The groups were matched regarding tumour size, receptor status, adjuvant chemotherapy and tumour differentiation. Tumour samples were analysed regarding expression of cyclin A, cyclin E and double-stained tumour cells using immunoflourescence staining and digital microscopy. Results. No differences were seen regarding expression of cyclin E or aberrant cyclin E in cases compared to controls. Discussion. We conclude that neither cyclin E nor aberrant cyclin E is a prognostic factor in low-risk node negative breast cancer patients.
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| 32. |
- Ahlström, Håkan, et al.
(author)
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An experimental model for pharmacokinetic studies of monoclonal antibodies in human colonic cancer
- 1987
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 26:6, s. 447-451
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Journal article (peer-reviewed)abstract
- An experimental model consisting of athymic rats carrying human colonic tumours from cell line LS 174T in both hind legs was used. 125I-labelled anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies were injected intra-arterially (i.a.), either alone (21 rats) or together with degradable starch microspheres (6 rats). As a control, an irrelevant antibody was injected i.a., alone (6 rats) or together with microspheres (3 rats). An intra-arterial injection was given on the side bearing one tumour in each rat, while the contralateral tumour served as an 'intravenous' control. The rats were submitted to external gamma measurements daily for four days. On the fourth day they were killed and pieces from the tumours and from various organs were examined by in vitro measurements. The results indicate strong expression of CEA in LS 174T cells grafted to athymic rats. No lasting enhancement of the tumour uptake was achieved by intra-arterial injection of antibodies as compared with the control tumours.
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| 33. |
- Ahlström, Håkan, et al.
(author)
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Enhanced uptake of intra-arterially injected anti-CEA monoclonal antibodies in human colonic cancer after mannitol infusion in an experimental model
- 1987
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 26:6, s. 453-458
-
Journal article (peer-reviewed)abstract
- In a previous report athymic rats carrying transplanted human colonic tumours from cell line LS 174T in both hind legs were injected intra-arterially (i.a.) with 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies. The i.a. injection was given on one side bearing a tumour in each rat, while the contralateral tumour served as an 'intravenous' control. In the same experimental model and treated in the same way, 10 rats were injected i.a. with anti-CEA monoclonal antibodies after an i.a. mannitol infusion. In both groups of rats external gamma measurements were performed daily for four days. On the fourth day the rats were killed and pieces of the tumours and of various organs were weighed and the activity was determined with a gamma-counter. The tumour uptake of antibodies was significantly enhanced after mannitol infusion.
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| 34. |
- Ahlström, Håkan, et al.
(author)
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The spatial distribution of parenterally administered monoclonal antibodies against CEA in a human colorectal tumour xenograft
- 1989
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 28:1, s. 81-86
-
Journal article (peer-reviewed)abstract
- A recently developed experimental model consisting of athymic rats carrying human colonic tumours from the cell line LS 174 T in both hind legs was used. 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies were injected either intra-arterially after a bolus injection of mannitol, or intra-peritoneally with or without mannitol. On the fourth day the rats were killed and pieces from the tumours and various organs were measured in a well scintillation counter. Tumour pieces were then submitted to autoradiography and immunohistochemistry for examination of the antibody distribution at the cellular level. In all examined tumours injected with anti-CEA antibodies, most of the antibodies were located in the periphery close to fibrovascular septa. It appears, in addition to the specificity of the antibody for the CEA, that the tumour vascular permeability and anatomy are of utmost importance for tumour targeting in this experimental model with the particular antibody used.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Albertsson, Per, 1964, et al.
(author)
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Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A.
- 2008
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:2, s. 293-300
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Journal article (peer-reviewed)abstract
- Low-dose continuous or metronomic chemotherapy with several agents can exert significant antiangiogenic effects, as shown in preclinical studies. Therapy of this kind is generally well tolerated compared with conventional chemotherapy with high, temporally spaced out bolus doses. A critical point emerges when the effects on angiogenesis of low-toxic metronomic doses of chemotherapeutics in preclinical studies are to be transferred to clinical protocols, as there is a risk that a virtually non-toxic dose might also be ineffective; clearly, dose-effect data are important. We therefore sought to investigate whether a dose-dependent response exists in metronomic vinblastine chemotherapy. The surrogate tumor-free rat mesentery model, allowing the study of antiangiogenic effects per se, was used. Following systemically administered metronomic chemotherapy, it closely reflects the indirectly assessed antiangiogenic and growth-retarding effects in a syngenic cancer model. VEGF-A, which is a central proangiogenic factor in most tumors, was administered i.p. to induce angiogenesis in the mesenteric test tissue and, using morphometry, the angiogenesis-modulating effects of vinblastine were assessed in terms of objective quantitative variables. We report that continuous vinblastine treatment with an apparently non-toxic dose (1.0 mg/kg/week or 0.143 mg/kg/day) for 10 days, and a dose that substantially inhibited the physiologic body-weight gain (2.0 mg/kg/week or 0.286 mg/kg/day) for 6 days, demonstrates a dose-response relationship; the high dose significantly suppresses angiogenesis. To our knowledge, no previous study has reported on a dose-dependent antiangiogenic effect by continuous or metronomic vinblastine treatment in a mammalian in vivo model.
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| 40. |
- Albertsson, Per, 1964, et al.
(author)
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Low-dose continuous 5-fluorouracil infusion stimulates VEGF-A-mediated angiogenesis.
- 2009
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:3, s. 418-25
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Journal article (peer-reviewed)abstract
- BACKGROUND: Tumor growth is angiogenesis-dependent. Animal studies have demonstrated that frequent administration of chemotherapeutics may have marked antiangiogenic effects and improved antitumor effects, with less severe toxic side-effects than intermittent maximum tolerated dose chemotherapy. Currently, research focused on low-dose antiangiogenic chemotherapy is increasing. We have recently reported that certain chemotherapeutics, including 5-fluorouracil (5-FU), may in fact stimulate angiogenesis in the tumor-free rat mesenteric window assay. The aim of the present study was to extend the investigation of the angiogenesis-modulating effects of 5-FU by prolonging the continuous infusion treatment time. METHOD: Angiogenesis was induced in the mesenteric test tissue in adult male Sprague-Dawley rats by i.p. injection of VEGF-A, which is a key angiogenic factor in most tumors. During the subsequent angiogenesis, 5-FU was delivered continuously for 14 days by an osmotic pump implanted subcutaneously. The angiogenic response was analyzed by morphometry in the mesenteric windows. RESULTS: The 14-days continuous infusion of 5-FU significantly stimulated angiogenesis. Thus the possibility that the previously reported surprising proangiogenic effect of 5-FU reflected an insufficiently long treatment period can be ruled out. CONCLUSION: The finding that continuously infused 5-FU is able to stimulate angiogenesis in the present rat model of angiogenesis warrants investigation of the mechanisms behind this unexpected finding. It may further have implications for the choice of antiangiogenic chemotherapeutic schedule used for cancer patients.
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