| 1. |
- Edgren, M, et al.
(författare)
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Angiogenic factors: vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) are not necessarily elevated in patients with advanced renal cell carcinoma.
- 2001
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Ingår i: Anticancer research. - 0250-7005. ; 21, s. 1423-
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Tidskriftsartikel (refereegranskat)abstract
- Serum analysis of Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (b-FGF) levels were studied in 53 patients with renal cell carcinoma (RCC). Approximately 2/3 of the patients had disseminated disease at diagnosis, the remainder had no evidence of metastases. The results confirmed that VEGF has a major role in the angiogenesis of RCC. No correlation was observed between VEGF and/or b-FGF and the presence or absence of metastases, nor was any correlation observed between VEGF and/or b-FGF and patient survival. Thus, to utilise VEGF and/or b-FGF as a tumour marker at the time of diagnosis to predict patients with a high risk of progression, where an adjuvant therapeutic approach would be of great value, seems to be limited. Not all patients with RCC exhibited elevated serum levels of VEGF and/or b-FGF. No correlation was observed between tumour stage and serum levels of these angiogenic peptides.
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| 2. |
- Edgren, M, et al.
(författare)
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Postoperative radiotherapy after prostatectomy can be associated with severe side effects.
- 2001
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Ingår i: Anticancer research. - 0250-7005. ; 21, s. 2231-
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Tidskriftsartikel (refereegranskat)abstract
- This retrospective study was initiated to evaluate the efficacy and side effects of post-prostatectomy external beam radiation therapy (XRT) with a short time interval between surgery and irradiation in patients with prostate adenocarcinoma. Sixteen patients were investigated. The overall results in this study were 3 deaths due to recurring disease and two relapses after an average follow-up of 60 months. Severe side effects were observed. Two patients required surgical intervention due to severe post-radiotherapy side effects. The reason for this could be the high dose delivered to peripheral organs and/or a too short time interval between surgery and postoperative XRT. The results of this study confirmed that postoperative XRT can improve local control frequency in prostate carcinomas. It is recommended that the time interval between surgery and postoperative radiotherapy should to be 3-6 month.
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| 3. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Antiangiogenic effect of metronomic paclitaxel treatment in prostate cancer and non-tumor tissue in the same animals: a quantitative study
- 2004
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Ingår i: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 112:3, s. 201-9
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Tidskriftsartikel (refereegranskat)abstract
- Well-tolerated continuous or metronomic chemotherapy can exert a marked antiangiogenic and thus superior antitumor effect compared with conventional high-dose, temporarily spaced-out chemotherapy, as shown in preclinical studies. There is, however, no means of directly assessing the antiangiogenic effect in a tumor, a serious impediment to assessing the effects of putative antiangiogenic chemotherapeutics or treatments. In an attempt to circumvent or minimize this impediment we studied the antiangiogenic effect of well-tolerated metronomic paclitaxel therapy in a surrogate tumor-free tissue that allows true quantitative analysis as well as in syngeneic At-1 prostate cancer in the same rat. This novel model allows an accurate comparison of the angiogenesis-modulating effect of chemotherapy in the two tissues to be made. The effect of chemotherapy on VEGF-A-mediated angiogenesis, a characteristic of most tumors, was assessed truly quantitatively by microscopic morphometry and image analysis in the tumor-free mesentery. The chemotherapy significantly suppressed VEGF-A-mediated angiogenesis in the mesentery to an extent that closely mirrored the significant increase in tumor necrosis measured morphometrically and the significant decrease in tumor growth rate. This finding opens an avenue to study quantitatively and systematically the antiangiogenic effect of chemotherapeutic modalities and treatments that approximately mirror their antiangiogenic effect in the At-1 tumor.
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| 4. |
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| 5. |
- Albertsson, Per, 1964, et al.
(författare)
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Chemotherapy and antiangiogenesis: drug-specific effects on microvessel sprouting
- 2003
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Ingår i: Apmis. - 0903-4641. ; 111:11, s. 995-1003
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are angiogenesis dependent. Some chemotherapeutics have been shown to be able to suppress angiogenesis and thus tumor growth in vivo at low, well-tolerated doses. Not much is known about the angiogenesis-modulating effects of chemotherapeutics in vivo, however. Microvessel sprouting is inherent to angiogenesis. Using the rat mesentery assay, we studied the effect of cyclophosphamide, doxorubicin and paclitaxel at a low, atoxic dose on the number of sprouts per unit tissue volume (No. SP) and their length (Le. SP) at the edge of the expanding network in VEGF165-mediated angiogenesis. A single dose of each cytotoxic drug was administered i.v. 7 days before the animals were sacrificed. Cyclophosphamide significantly lengthened the shortest Le. SP and shortened the longest Le. SP, doxorubicin did not significantly affect Le. SP, whereas paclitaxel significantly shortened both the shortest and the longest Le. SP. No correlation was found between the present results and the distinctly drug-specific results of microvessel segment number and length analyzed within central parts of the same expanding network. To our knowledge, this is the first quantitative report on the effect of chemotherapy on angiogenesis sprouting in vivo. Collectively, the data suggest that cyclophosphamide, doxorubicin and paclitaxel at a non-toxic dose primarily target different intrinsic components of the angiogenic cascade, leading to distinctly drug-specific effects.
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| 6. |
- Bredenberg, S., et al.
(författare)
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In vitro and in vivo evaluation of a new sublingual tablet system for rapid oromucosal absorption using fentanyl citrate as the active substance
- 2003
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Ingår i: Eur J Pharm Sci. - 0928-0987. ; 20:3, s. 327-34
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Tidskriftsartikel (refereegranskat)abstract
- Oromucosal delivery of drugs promotes rapid absorption and high bioavailability, with subsequent almost immediate onset of pharmacological effect. However, many oromucosal delivery systems are compromised by the possibility of the patient swallowing the active substance before it has been released and absorbed locally into the systemic circulation. This paper introduces a new tablet system for sublingual administration and rapid drug absorption. The tablet is based on interactive mixtures of components, consisting of carrier particles partially covered by fine dry particles of the drug, in this case fentanyl citrate. In the interests of increasing retention of the drug at the site of absorption in the oral cavity, a bioadhesive component was also added to the carrier particles. Tablets containing 100, 200 and 400 microg of fentanyl were tested both in vitro and in vivo. The tablets disintegrated rapidly and dissolution tests revealed that fentanyl citrate was dissolved from the formulation almost instantly. Plasma concentrations of fentanyl were obtained within 10 min, with no second peak. These results indicated that the bioadhesive component prevented the fentanyl from being swallowed (the fraction swallowed was considered smaller compared to other mucosal delivery systems), without hindering its release and absorption. This new sublingual tablet formulation may also hold potential for other substances where a rapid onset of effect is desirable.
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| 7. |
- Edgren, M, et al.
(författare)
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Estramustine a radio sensitising agent.
- 2000
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Ingår i: Anticancer research. - 0250-7005. ; 20:4, s. 2677-80
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Tidskriftsartikel (refereegranskat)abstract
- The present study revealed that estramustine acts as a radio sensitising agent on the human renal cell cancer cell lines, A498 and CAKI-2. In vitro experiments used the Bürker chamber technique. Both cell lines were markedly resistant to external beam irradiation. While pretreatment of the cell cultures with estramustine prior to external beam irradiation revealed an arrest of cell growth in both cell lines. The results of this study suggest that estramustine could be utilised as a radiosensitizing agent. This in turn could open a new method for the management of patients with advanced renal cell carcinoma (RCC).
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| 8. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Anorectal function after modern conformal radiation therapy for prostate cancer: a pilot study
- 2002
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Ingår i: Tech Coloproctol. - 1123-6337. ; 6:2, s. 101-4
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated whether, and if so to what extent, radiotherapy applied on a series of patients with prostate cancer influenced the patient's bowel habits and anorectal function. Ten consecutive patients participated in the study. The median age of the patients was 74 years (range, 61-71) and the average follow-up period was 22 (range, 15-28) months. Four patients were irradiated using external beam radiotherapy (2 Gy/day for a total of 70 Gy); 6 patients were irradiated with a combination of external beam radiotherapy (50 Gy, 2 Gy/day) and high dose rate brachytherapy (two 10-Gy fractions). Upon interview, patients disclosed characteristic functional disturbances such as urgency with occasional accidents, faecal soiling and spotting of underwear. Involuntary release of gas was another embarrassing problem. One or more of these problems were present in half of the patients. Endoscopy disclosed signs of mild proctitis. Sphincter pressure, rectal capacity and the volume threshold for appreciation of defecation urge were all significantly lower in patients than in 10 age-matched controls. In conclusion, disturbances of anorectal function with imperfection of incontinence still occur so some extent despite improved precision, and reduced margins offered by the modern conformal radiation therapy of prostate cancer. Anal sphincter function, the reservoir capacity of the rectum and its sensory function are adversely affected and radiation proctitis with rectal fibrosis and damage of the extrinsic innervations of the anal sphincters appear to be the principal causative factors. Although conformal radiotherapy together with better positioning may be two substantial improvements of modern radiotherapy, further improvements are needed.
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| 9. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Chemotherapy and antiangiogenesis--drug-specific, dose-related effects
- 2003
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Ingår i: Acta Oncol. - 0284-186X. ; 42:4, s. 294-303
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Tidskriftsartikel (refereegranskat)abstract
- Dose-response effects of fluorouracil, paclitaxel, doxorubicin, cisplatin, methotrexate, cyclophosphamide and etoposide on VEGF165/164-mediated angiogenesis using the rat mesenteric-window angiogenesis assay are reported. VEGF is a pivotal pro-angiogenic factor in most tumors. Microvessel spatial extension, density, pattern formation and segment length were assessed quantitatively and objectively. A single i.v. injection of each drug was given at a low, intermediate or high dose, 7 days before sacrifice. All the drugs elicited significant responses in terms of one or more measured variables. Only paclitaxel, doxorubicin and cyclophosphamide significantly suppressed the overall angiogenic response (p < or = 0.0001, p < or = 0.0002 and p < or = 0.05, respectively), however. Taking toxicity into account, paclitaxel was more potent in inhibition of angiogenesis than the other agents. No clear correlation was found between drug half-life, the degree of toxic effects (in terms ofbody weight changes) and the antiangiogenic effect. The antiangiogenic effects were distinctly drug specific.
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| 10. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Postoperative radiotherapy after prostatectomy--a review
- 2003
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Ingår i: Scand J Urol Nephrol. - 0036-5599. ; 37:1, s. 10-5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The management of prostate adenocarcinomas using postoperative irradiation is a controversial question. The purpose of this study was to review the literature on the subject. MATERIAL AND METHODS: A total of 417 articles dealing with postoperative radiotherapy after radical prostatectomy in English literature (1990-2002) were reviewed in aspects of effect on survival, time of irradiation, risk factors, dose and technique and side effects. RESULTS AND DISCUSSION: No randomised studies have been performed and therefore no definitive conclusive data can be made concerning the efficiency of the concept. However, postoperative radiotherapy appears to increase local control preferably in pT3/4 prostatic carcinomas with seminal vesicles involvement and/or positive margins and/or high Gleason score and high postoperative PSA level. It has not been shown to improve survival. Severe side effects are reported in a low frequency. However, postoperative irradiation can cause severe side effects and postoperative adjuvant/salvage treatments should be delivered earliest 3-6 months after surgery and the total dose delivered to the prostate bed should be 65-70 Gy. Postoperative radiotherapy induces improved local control in patients with positive surgical margins and in patients with a local relapse, preferably if the tumour is small (i.e. PSA <1-2 ng/mL).
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