1.
Albertsson, Per, 1964, et al.
(författare)
Chemotherapy and antiangiogenesis: drug-specific effects on microvessel sprouting
2003
Ingår i: Apmis. - 0903-4641. ; 111:11, s. 995-1003
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.
2.
Bredenberg, S., et al.
(författare)
In vitro and in vivo evaluation of a new sublingual tablet system for rapid oromucosal absorption using fentanyl citrate as the active substance
2003
Ingår i: Eur J Pharm Sci. - 0928-0987. ; 20:3, s. 327-34
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.
3.
Lennernäs, Bo, 1963, et al.
(författare)
Chemotherapy and antiangiogenesis--drug-specific, dose-related effects
2003
Ingår i: Acta Oncol. - 0284-186X. ; 42:4, s. 294-303
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.
4.
Lennernäs, Bo, 1963, et al.
(författare)
Postoperative radiotherapy after prostatectomy--a review
2003
Ingår i: Scand J Urol Nephrol. - 0036-5599. ; 37:1, s. 10-5
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).
