| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
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| 5. |
- Silén, A, et al.
(författare)
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Evaluation of the UBC test in the urine of healthy individuals, patients with benign disorders and urinary bladder cancer.
- 2000
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Ingår i: Oncology reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 7:6, s. 1269-74
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Tidskriftsartikel (refereegranskat)abstract
- Using the UBC test, the specificity, sensitivity and prognostic information were evaluated in patients with recently diagnosed transitional cell carcinoma (TCC) and in a control group consisting of apparently healthy individuals and individuals with benign disorders. Frozen urine samples from the 485 individuals in the control group and 100 newly diagnosed TCC patients were analyzed with the UBC test, specific for epitopes on cytokeratin fragments released from the urothelial cells. All the samples were analyzed and corrected for creatinine. No significant concentration difference was found between males and females (p=0.65) and there was no age dependent relation. The median concentration for the entire control group was estimated at 3.7 microg/g and the 95th percentile was calculated at 53.0 microg/g. The apparently healthy individuals in the control group had a median value of 3.4 microg/g with a 95th percentile of 24.3 microg/g. An increased frequency of elevated UBC concentrations was found in some benign disorders e.g., anemia, thyroid disorders, diabetes mellitus, hyperlipemia, urosepsis and cystitis. Patients with superficial tumors exhibited a 66% sensitivity (at 95% specificity), and the UBC concentrations did not differ statistically (p=0.16) from those patients with muscle invasive lesions with a 52% sensitivity. When the UBC concentrations were related to histopathological grade, a significant concentration difference (p<0.004) was found between low grade tumors (sensitivity 41%) and high grade tumors (sensitivity 72%). Survival analysis showed that patient with muscle invasive tumors, high-grade tumors and high UBC concentrations have a significantly reduced survival (five-year survival was estimated to 30%, 35% and 30% respectively) compared to patients with superficial tumors, low-grade tumors or low UBC concentrations (five-year survival, 60%, 85% and 75% respectively). The UBC test showed good accuracy and repeatability. Clinically the test could assist in tumor grading and the detection of recurrent disease, which in turn could assist in treatment selection for the individual patient and possibly improve prognosis.
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| 6. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Silicon diodes as detectors for backscatter radiation in photon fields.
- 2001
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Ingår i: Oncology reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 8:1, s. 181-3
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the use of unencapsulated silicon semiconductor detectors for backscatter radiation detection. The results were compared with Monte Carlo (MC) calculations modelling the experimental set-up. A special diode was manufactured, which was designed so that it allowed the positioning of different materials in close contact with the detector surface. Polymethylmethacrylate (PMMA), Pb, Ti and Fe (stainless steel) were used as backscatter materials. The diode signal was measured by integrating the current when irradiating the diode with an equal photon fluence obtained from a medical Co-60 source. When compared to the signal with PMMA as backscatter material the increase in signal was 21%, 27% and 73% for Ti, Fe and Pb, respectively. This is in reasonable agreement with the MC calculations, when taking the effective measurement depth in the Si diode detector into account.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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