Search PubMed⌕ Search

Biomedical subjects

G Storme

Publications and source records attributed to G Storme.

66 records · Page 4Linked to original sources
PubMed1980

Effect of anticancer agents on directional migration of malignant C3H mouse fibroblastic cells in vitro.

Invasion of malignant cells was considered as a target for therapy. The effect of various anticancer agents, which were known to permit or to prevent invasion in vitro, on the growth and on the directional migration of virally transformed malignant C3H mouse fibroblastic cells (MO4) was examined. The increase of the diameter of spheroidal aggregates of MO4 cells in individual shaker culture was used as an index of growth. The mean diameter of the circular area covered by cells migrating from an aggregate explanted on glass, the number of cells in the periphery of this area, the height of the central part of the aggregate, the microcinephotographic aspect of migrating cells, and the immunocytochemistry of the cytoplasmic microtubular complex were considered as indices of directional migration. Ionizing radiation (5,000 and 20,000 R), and 5-fluorouracil (0.1, 0.5, and 1 microgram/ml), known to permit invasion, inhibited growth but allowed directional migration. Nocodazole (0.1 and 1 microgram/ml), known to prevent invasion, interfered with both growth and directional migration. These observations showed that various agents which affected the growth of aggregates of MO4 cells had different effects on the directional migration of these cells; they suggested that proliferation and migration were unrelated cellular activities. The assay for directional migration of cells from a spheroidal aggregate explanted on glass is proposed for the screening of potential antiinvasive agents.

Animals↗
PubMedDate not supplied

The influence of the ambient temperature on tumour growth, metastasis and survival in mice.

The effect of ambient temperature was analysed on the behaviour of MO4 cells which are malignant, invasive and metastasizing C3H mouse fibroblastic cells when implanted in the tail of the syngeneic animal. Raising the ambient temperature to 28 degrees C increases growth of the primary tumour, incidence of metastases and shortens survival. Lowering the ambient temperature to 13 degrees C prevents all these phenomena. Measurements at the implantation site show that the temperature of the tail remains in a range +/- 2-3 degrees C in accordance with the environment. From these results we conclude that room temperature may be important when experiments are performed in vivo.

Animals↗
PubMedDate not supplied

[Conformal radiotherapy: tomotherapy].

Conformal radiation therapy allows the possibility of delivering high doses at the tumor volume whilst limiting the dose to the surrounding tissues and diminishing the secondary effects. With the example of the conformal radiation therapy used at the AZ VUB (3DCRT and tomotherapy), two treatment plans of a left ethmoid carcinoma will be evaluated and discussed in detail. The treatment of ethmoid cancer is technically difficult for both radiation therapy and surgery because of the anatomic constraints and patterns of local spread. A radiation therapy is scheduled to be delivered after surgical resection of the tumor. The treatment plan for the radiation therapy was calculated on a three-dimensional (3D) treatment planning system based on virtual simulation with a beam's eye view: George Sherouse's Gratis. An effort was made to make the plan as conformal and as homogeneous as possible to deliver a dose of 66 Gy in 33 fractions at the tumor bed with a maximum dose of 56 Gy to the right optic nerve and the chiasma. To establish the clinical utility and potential advantages of tomotherapy over 3DCRT for ethmoid carcinoma, the treatment of this patient was also planned with Peacock Plan. For both treatment plans the isodose distributions and cumulative dose volume histograms (CDVH) were computed. Superimposing the CDVHs yielded similar curves for the target and an obvious improvement for organs at risk such as the chiasma, brainstem and the left eye when applying tomotherapy. These results have also been reflected in the tumor control probabilities (equal for both plans) and the normal tissue complication probabilities (NTCP), yielded significant reductions in NTCP for tomotherapy. The probability of uncomplicated tumor control was 52.7% for tomotherapy against 38.3% for 3DCRT.

Ethmoid Bone↗
PubMedDate not supplied

Increasing peak levels of vinblastine given in repeated divided doses.

Pharmacokinetics of vinblastine were assayed in 9 patients, using a high pressure liquid chromatography method. Patients were treated in three different ways: the first 3 patients received bolus injections of vinblastine at a fixed dose of 2 mg/day for 5 consecutive days. Three other patients were treated with 3 mg/m2 vinblastine as a bolus injection on day 1, day 3 and day 8. The remaining 3 patients received a bolus injection of vinblastine of 6 mg/m2 on day 1, day 8 and 15. Blood samples were taken on days 1, 3 and 5 for the first group and on every treatment day for the other groups. The early phase peak levels obtained during the 5 day-treatment increased progressively during repeated treatments, probably due to decreased central compartment volumes and not to drug accumulation. There was no relation between vinblastine levels and orosomucoid levels. The rise in peak level was less predictable during the other methods of treatment (once or twice weekly). This observation calls attention to the necessity of performing drug level monitoring at very early time points, as increasing peak levels during repeated administration may explain unexpected toxicities.

Adult↗
PubMedDate not supplied

Not the presence but the synthesis of HSPS correlates with thermotolerance in a fibrosarcoma MO4 cell-line.

This study reports the induction of heat shock proteins (hsps) and thermotolerance in a MO4 cell line. An enhanced synthesis of hsp68, hsp70 and hsp90 was observed. After 6 hrs, the synthesis of hsp68 and hsp70 decreased to the control value. Hsp90 synthesis was absent after 10 hrs. However, hsps were found to be stable for longer periods of time (more than 48 hrs). A coupled study of hsps and SF demonstrated that an induction of hsps were followed by a change in the slope of the survival curve. Thermotolerance, as expressed by the observed SF after a second heating, is only present during the first 4 hrs and decayed between 4 and 8 hrs. We could not find a correlation between the presence of hsps and thermotolerance, but only between the synthesis of hsps and thermotolerance in MO4 cells.

Animals↗
PubMedDate not supplied

[Breast-sparing surgery in T1 breast carcinoma].

31 female patients with a T1 No N1a Mo breast tumour (diameter smaller or equal to 2 cm) were treated by segmental resection with complete axillar dissection, followed by radiotherapy. Chemotherapy was given in any case of axillary lymph node involvement. The mean follow-up period was 44 months. Absolute survival is 100%. One patient (3%) developed distant metastasis, 2 patients (6%) had a loco-regional recurrence and 3 presented with a metachronous tumour in the contralateral breast. 97% of the patients are actually alive and free of disease.

Adult↗
PubMedDate not supplied

The effect of pentagastrin on the directional migration of colon adenocarcinoma cells in vitro.

The centrifugal spreading of multicellular aggregates from a DMH induced colon adenocarcinoma cell line from rats was observed in vitro. Various concentrations of pentagastrin were added to the culture medium. Controls included medium alone or culture medium containing different concentrations of either NH4OH or NaOH that were needed to dissolve the pentagastrin. The migration index, the total surface area occupied by the cells after 7 days, and the cell density of the culture were measured. Using 10 micrograms/ml of pentagastrin, the migration idex and the area covered by the cells were increased (P less than 0.01) while the cell density was not. Inhibition of cell division through addition of 5 fluoro-uracil to the culture medium abolished the stimulating effect of pentagastrin although the centrifugal migration was not suppressed by the antimetabolite. These data indicate that a supraphysiological concentration of pentagastrin can stimulate the spreading of colon cancer cell aggregates in vitro by enhanced proliferation.

Adenocarcinoma↗
PubMedDate not supplied

Interaction between vinblastine and ionizing radiation in the mouse MO4 fibrosarcoma in vivo.

The effect of combining vinblastine (VLB) and ionizing radiation (IR) on tumor response was investigated in CDF1 mice bearing the MO4 mouse fibrosarcoma. Favorable interactions were assumed to occur if VLB treatment caused accumulation of cells in metaphase (M-)phase at the time of IR. High pressure liquid chromatography (HPLC) measurements showed that VLB administered at 2.0 mg/kg (0.4 maximal tolerated dose, MTD) was taken up rapidly by the tumor in vivo, and that sufficient concentrations of VLB were achieved to cause blocking of tumor cells in M-phase. However, different treatment schedules of the combination of 2.5 mg/kg VLB (0.5 MTD) and 10 Gy IR resulted in additive tumor responses. The best therapeutic response was observed when IR was given 6 hours after intravenous injection of VLB. In order to increase the therapeutic response, we attempted to enhance the accumulation of cells in M-phase by treating mice with VLB at the MTD. The maximum percentage of tumor cells that could be accumulated in mitosis by a single intravenous bolus of VLB at the MTD was around 13%. The results show that this will probably be insufficient for significant IR enhancement.

Animals↗
PubMedDate not supplied

DNA breakage, cytotoxicity, drug accumulation and retention in two human ovarian tumor cell lines AZ224 and AZ364 treated with adriamycin, modulated by verapamil.

We investigated the cytotoxicity of adriamycin in two human ovarian tumor cell lines, AZ224 and AZ364, by the MTT-test and we analysed the formation of DNA single-strand (SSB) and double-strand breaks (DSB) by means of the alkaline and neutral elution technique. The AZ364 cell line was 15 times more resistant to ADR (ID50 = 10.0 micrograms/ml) than the AZ224 cell line (ID50 = 0.66 microgram/ml) after 1hr of drug exposure. Immediately after exposure, we observed a biphasic dose response for SSB in the AZ224 cells over a concentration range of 0.1 to 32.0 micrograms/ml, while practically no DSB were found. Upon drug removal and incubation in drug-free medium, full repair of SSB was observed for an ADR concentration of 1 microgram/ml. On the contrary, the DSB became significantly increased for all tested concentrations and persisted as observed after 3hr and 7hr in drug-free medium. The resistant cell line AZ 364 showed consistently less DNA breakage than the AZ 224 cell line. This inherent difference in sensitivity to ADR could, however, not be explained on the basis of the cellular pharmacokinetics of the drug. Verapamil induced a 3 to 4 fold potentiation of the ADR cytotoxicity in both cell lines after continuous exposure and was associated with an increase in DNA-breakage. The results of our study confirm that there is a lack of correlation between cytotoxicity of ADR and DNA strand breakage immediately after 1 hr of drug exposure. Instead, we emphasize the importance of the formation, extent and persistence of protein-associated DSB upon drug removal to the cytotoxic action of ADR in vitro.

DNA Damage↗
PubMedDate not supplied

5'-Nor-anhydrovinblastine (Navelbine) has an anti-invasive effect on MO4 mouse fibrosarcoma cells in vitro and in vivo.

5'-nor-anhydrovinblastine (Navelbine) is a hemisynthetic Vinca alkaloid for which a selectivity for mitotic microtubules has been demonstrated. In previous studies, we have demonstrated an anti-invasive effect of other Vinca alkaloids. Here the results of in vitro and in vivo assays concerning the effect of 5'-nor-anhydrovinblastine on growth and invasion of MO4 cells are presented. It is demonstrated that at cytostatic concentrations, 5'-nor-anhydrovinblastine also has an anti-invasive effect.

Animals↗