| 1. |
- Gullbo, Joachim, et al.
(författare)
-
Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo.
- 2004
-
Ingår i: Investigational new drugs. - 0167-6997. ; 22:4, s. 411-20
-
Tidskriftsartikel (refereegranskat)abstract
- The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity.
|
|
| 2. |
- Malmberg, Per, 1974, et al.
(författare)
-
Subcellular localisation of cholesterol and phosphocholine with pattern-recognition-imaging-TOF-SIMS
- 2004
-
Ingår i: Spectroscopy. ; 18:4, s. 503-512
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular ions of cholesterol, and its fragments, and phosphocholine fragments of phospholipids, were localized in single cells with a resolution of <1 μm. This is the first example of subcellular localisation of membrane lipids with pattern-recognition, imaging time-of-flight secondary ion mass spectrometry (PRITS) here utilized for identification and subcellular localisation of cholesterol and phosphocholine in PMN leukocytes. Cell imprints were produced by transferring the cell constituents of freeze-dried cells to a silver foil, and the silver surface was analyzed by TOF-SIMS. TOF-SIMS spectra were recorded by scanning the primary ion beam over the analysis area and acquiring a positive mass spectrum of the ions leaving the surface. Data were collected at either high mass resolution m/Δm>7000 or high lateral resolution. High mass resolution spectra were recorded on reference samples of pure cholesterol and phosphatidylcholine. Characteristic fragment peaks and the silver cationised quasimolecular ion [M+Ag]+ were selected as a pattern for the identification of the lipids in TOF-SIMS images of surface-adhering leukocytes. The localisation of membrane lipids showed lateral heterogeneity over the cell surface.
|
|
