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Biomedical subjects

O Dahl

Publications and source records attributed to O Dahl.

At least 55 records · Page 3Linked to original sources
PubMed1997

Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro.

Paclitaxel (Taxol), an anti-cancer drug derived from Taxus species, was tested for its anti-migrational, anti-invasive and anti-proliferative effect on two human glioma cell lines (GaMg and D-54Mg) grown as multicellular tumour spheroids. In addition, the direct effect of paclitaxel on glioma cells was studied using flow cytometry and scanning confocal microscopy. Both cell lines showed a dose-dependent growth and migratory response to paclitaxel. The GaMg cells were found to be 5-10 times more sensitive to paclitaxel than D-54Mg cells. Paclitaxel also proved to be remarkably effective in preventing invasion in a co-culture system in which tumour spheroids were confronted with fetal rat brain cell aggregates. Control experiments with Cremophor EL (the solvent of paclitaxel for clinical use) in this study showed no effect on tumour cell migration, cell proliferation or cell invasion. Scanning confocal microscopy of both cell lines showed an extensive random organization of the microtubules in the cytoplasm. After paclitaxel exposure, the GaMg and the D-54Mg cells exhibited a fragmentation of the nuclear material, indicating a possible induction of apoptosis. In line with this, flow cytometric DNA histograms showed an accumulation of cells in the G2/M phase of the cell cycle after 24 h of paclitaxel exposure. After 48 h, a deterioration of the DNA histograms was observed indicating nuclear fragmentation.

Adult↗
PubMed1997

Fibrosarcoma in children--a rare tumour with long-term survival even with advanced disease--a report of 3 cases.

Fibrosarcoma is a rare tumour in children. The potential of malignancy has been questioned. We present three cases of fibrosarcoma in children . The follow-up periods range from 10 to 37 years. The first patient had pulmonary metastases at the time of diagnosis in 1958. The primary tumour in fossa ischio-rectalis was resected in 1960. Lung metastases were resected in 1960 and 1989. Radiotherapy was given in 1992. He is still alive with metastases 37 years after the first manifestation of disease. The second patient had a primary tumour and several local recurrences in the mandible. He is alive without evidence of disease 4 years after resection of pulmonary metastases and 21 years after resection of the primary tumour. The third patient has no signs of recurrence or metastatic spread 10 years after a wide excision of subcutaneous tumours of the left upper arm. The cases demonstrate a special tumour-entity of low-grade malignancy, which show a good prognosis and a wide spectrum of biological behaviour.

Abdominal Neoplasms↗
PubMed1996

Use of the vasodilator sodium nitroprusside during local hyperthermia: effects on tumor temperature and tumor response in a rat tumor model.

PURPOSE: The effect of a decrease in the mean arterial blood pressure (MAP) induced by sodium nitroprusside (SNP) on the tumor temperature during hyperthermia (HT), and on the cytotoxic effect of HT, was studied in the BT4An tumor transplanted to the hind limb of BD IX rats. Experiments with two different anesthetics, pentobarbital and the midazolam/fentanyl/fluanisone combination (MFF), were performed to secure reliable conclusions. METHODS AND MATERIALS: In the tumor response experiments local waterbath HT at 44.0 degrees C was given for 60 min. Sodium nitroprusside was administered as a continuous intravenous infusion to lower the MAP to 60 or 80 mmHg during HT. In two other experiments the temperature at the base of the tumor during HT was measured before and during SNP infusion. In animals without tumor the temperature was measured subcutaneously on the foot during HT with or without SNP-induced hypotension. RESULTS: When SNP was given to lower the MAP to 60 mmHg during HT in MFF anesthetized animals, the median tumor growth time (TGT) was 70 days, compared to 14.5 days in the HT alone group. The corresponding figures were 127 and 12.1 days with pentobarbital anesthesia. In the HT + SNP group, more than 40% cure was observed in both experiments. No cures were seen in any of the other groups. Hyperthermia alone prolonged the TGT slightly, whereas SNP given alone had no effect, compared to controls. When the MAP was lowered to 80 mmHg by SNP infusion during HT (MFF anesthesia), the median TGT was 19.9 days, which was significantly longer than that in the HT alone group (10.9 days). In the MAP range from 60 to 120 mmHg, a nearly linear relationship between the MAP and the tumor temperature was found during HT in MFF anesthetized animals. With both anesthetics, the median temperature at the base of the tumor was about 0.8 degrees C higher during HT when the MAP was lowered to 60 mmHg by SNP. In animals without tumors, the temperature subcutaneously on the foot was 0.3 and 0.4 degrees C higher during SNP infusion in the MFF and pentobarbital group, respectively. CONCLUSION: We have developed a small animal model in inbred rats feasible for exploring the influence of a stable blood pressure reduction induced by SNP, on the effect of HT given alone or in combination with other treatment modalities to a transplantable tumor. The greatly increased cytotoxic effect of local waterbath HT in the present tumor response experiments is probably a consequence of increased tumor temperature during SNP infusion.

Animals↗
PubMed1996

NMR investigations of duplex stability of phosphorothioate and phosphorodithioate DNA analogues modified in both strands.

Duplex formation from the self-complementary 12mer d(CGCGAATTCGCG) (Dickerson dodecamer) in which all phosphodiester linkages were replaced by phosphorothioate or phosphorodithioate linkages was studied using variable-temperature 1H and 31P NMR spectroscopy. Melting temperatures of the dodecamer, measured spectrophotometrically, showed significant decrease upon sulfur substitution (Tm 49 degrees C for the phosphorothioate and 21 degrees C for the phosphorodithioate, compared with 68 degrees C for the unmodified oligomer, in 1 M salt). Hyperchromicity observed upon melting of the dithioate was surprisingly low. NOESY spectra of the monothioate showed a cross-peak pattern characteristic for a right-handed duplex. Imino proton resonances of the duplex, shown by the mono- and the dithioate, were similar to those of the parent compound. In spite of monophasic melting curves, temperature dependence of the imino proton resonances and phosphorus resonances of the phosphorodithioate indicated heterogeneity with respect to base-pairing, compatible with the presence of a hairpin loop. Relaxation times (T1) of the imino protons in the phosphorothioate, determined by the saturation recovery method, were considerably shorter than in the unmodified oligomer. Base-pair lifetimes in the unmodified Dickerson dodecamer, determined by catalyst-dependent changes in relaxation rates of imino protons, were in the range of 2-30 ms at 20 degrees C. Strongly reduced base-pair lifetimes were found in the phosphorothioate analogue.

DNA↗
PubMed1996

[Chemotherapy in colorectal cancer. Recommendations of the Norwegian Gastrointestinal Cancer Group].

The scientific documentation for fluorouracil-based chemotherapy in patients with colorectal cancer has increased during recent years, both for the adjuvant primary situation and in recurrent and metastatic disease. In the case of operable colorectal cancer (stage Dukes B and C), the patients should be included in the ongoing randomized trial on use of fluorouracil and levamisol. In advanced disease, fluorouracil combined with calcium folinate may have palliative effects in terms of relief of symptoms, improved quality of life, delay of onset of symptoms and probably also prolonged survival in 40-50% of the patients, without serious toxicity. In many cases, however, the patient should not be given chemotherapy.

Chemotherapy, Adjuvant↗
PubMed1996

[Treatment of fixed, primarily non-resected rectal cancer. Recommendations from Norwegian Gastrointestinal Cancer Group].

In most cases (70%), fixed rectal cancers are primarily non-resectable, and of the ones that are resected, local recurrence will occur in 50-70%. The same trend, but less pronounced, is also seen for partly fixed or tethered tumours. High-dose irradiation (45-60 Gy) has been reported to yield resectability rates up to 70%, with 17% local recurrences and a 5-year disease-free survival of up to 60-70%. Combined chemotherapy and sequential radiation therapy, hyperthermia or addition of intra-operative radiotherapy, have shown promising results, but no randomized studies have been published comparing the different treatment modalities. Surgery should be performed 4-6 weeks after preoperative treatment. Resectability can only be determined by exploratory laparotomy and serious attempts to remove the tumour-bearing segment by anatomic dissection.

Combined Modality Therapy↗
PubMed1996

Interaction between microwave-induced brain hyperthermia and high dose rate radiation in the BT4 An brain glioma in rats.

The cerebral BT4An glioma model in BD IX rats was used to study the effect of hyperthermia given in combination with radiotherapy (thermoradiotherapy) in the treatment of brain tumours. A single treatment with high dose rate radiation was given to a local brain field. Local brain hyperthermia was given at 42.4 degrees C for 45 min by externally applied microwaves (700 MHz), immediately before radiotherapy (10 Gy). In a pilot study, thermoradiotherapy increased the median life span with 20 days compared to controls, which was significantly better than that observed after radiotherapy alone (7 days). In an extended experiment the corresponding figures for thermoradiotherapy, hyperthermia alone and radiotherapy alone were 12.5, 3.5, and 3.5 days, respectively. Thermoradiotherapy was significantly better than radiotherapy and hyperthermia alone. There was no acute mortality in these experiments. Neurological side-effects were infrequent, of slight degree and reversible. The present study shows that a survival benefit of adding hyperthermia to radiotherapy can be achieved without unacceptable neurological side-effects in an animal glioma model.

Animals↗
PubMed1995

Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology.

The value of hyperthermia as an adjuvant to radiotherapy in patients with malignant melanoma was studied in a European multicentre trial. 134 metastatic or recurrent lesions of malignant melanoma in 70 patients were randomly assigned to receive radiotherapy (three fractions of 8 Gy or 9 Gy in 8 days) alone or followed by hyperthermia (43 degrees C for 60 min). Overall, the 2-year actuarial local tumour control was 37 (SE 5)%. Univariate analysis showed a beneficial effect of hyperthermia (radiation alone 28% vs combined treatment 46%, p = 0.008) and radiation dose (24 Gy 25% vs 27 Gy 56%, p = 0.02), but no effect of tumour size (< or = 4 cm 42% vs > 4 cm 29%, p = 0.21). Cox multivariate regression analysis showed the most important prognostic variables to be hyperthermia (odds ratio for 2-year local control 1.73 [95% CI 1.07-2.78], p = 0.023), tumour size (0.91 [0.85-0.99], p = 0.05), and radiation dose (1.17 [1.01-1.36], p = 0.05). Addition of heat did not significantly increase acute or late radiation reactions. Heating was well tolerated, but because of difficulties with equipment only 14% of treatments achieved the protocol objective. The overall 5-year survival rate was 19%, but 38% of the patients for whom all known disease was controlled survived 5 years. Adjuvant hyperthermia significantly improved local tumour control when applied in association with radiation in treatment of malignant melanoma. Successful local treatment of patients with a single or a few metastatic malignant melanoma lesions has significant curative potential.

Adult↗
PubMed1995

The use of non-proven therapy among patients treated in Norwegian oncological departments. A cross-sectional national multicentre study.

A national multicentre study was performed to investigate the prevalent use of "alternative medicine", here called "non-proven therapies (NPT)", applied among Norwegian cancer patients. Of 911 patients invited to take part in the study, 642 were included in the analysis. Demographic characteristics were collected for all patients. The participating physicians gave information about the patients' clinical characteristics. Among 630 evaluable patients, 20% had been or were present users of NPTs for their oncological disease. The preferred methods were healing by hand and faith healing. Herbs, vitamins, diets and Iscador were other popular methods. As many as 40% of the users of NPTs had used NPTs earlier for non-malignant diseases. Elderly patients were less likely to use NPTs. Use was high in the northern part of Norway.

Adolescent↗
PubMed1995

A century with hyperthermic oncology in Scandinavia.

The hyperthermic research during the last 100 years is reviewed with the aim to describe a research activity which has been performed in parallel to and associated with the development of radiation oncology. Basic and clinical research in several Scandinavian centres has made major international contributions to the establishment of a rationale for and implementation of hyperthermia as a combined modality treatment with chemotherapy or radiation in oncology. At the same time it has been demonstrated that collaboration and integration easily could be performed within the Scandinavian centres. Hyperthermic oncology is therefore a typical example of how research involving both biological, physical/engineering, and clinical skills in a proper environment can create valuable results.

History, 20th Century↗
PubMed1994

Preparation of oligodeoxyribonucleoside phosphorodithioates by a triester method.

A method to prepare thymidine phosphorodithioate dimers (ref. 1) has been extended to allow the preparation of oligo-2'-deoxyribonucleotide phosphorodithioates containing all four bases. The method is suitable for large-scale synthesis and gives phosphorodithioates without phosphorothioate impurities (31P nmr, detection limit 0.5 to 1%). Oligonucleotides up to octamers which contain -0-(PS2-)-0- linkages at all positions have been prepared by block synthesis in solution. The phosphorodithioate linkage is introduced by the reaction of a 5'-O, N-protected nucleoside (or oligonucleotide) with a dithiophosphorylating agent RSP(S)(ODhbt)2, R = 2,4-dichlorobenzyl, Dhbt = 3,4-dihydro-4-oxo-benzotriazin-3-yl, followed by coupling of the product to a 3'-O,N-protected nucleoside (or oligonucleotide). This method gives pure protected oligodeoxyribonucleoside phosphorodithioates, and phosphorothioate linkages are only introduced if contact with conc. aqueous ammonia during or after deblocking is unduly prolonged.

Cross-Linking Reagents↗
PubMed1994

Do acute side-effects during radiotherapy predict tumour response in rectal carcinoma?

Patients given preoperative radiotherapy (31.5 Gy in 18 fractions) in a prospective, randomized trial of presumably operable rectal adenocarcinoma, were examined for a possible relation between bowel toxicity manifested as diarrhoea, and tumour size in the operative specimen, in addition to recurrence rate. The group requiring drugs for diarrhoea had significantly smaller tumours at surgery (2.5 cm versus 3.5 cm, p < 0.05). Patients without significant radiation-induced diarrhoea had also more recurrences (37.5% against 14.3%, p = 0.01). The disease-specific survival rate was also significantly better (p = 0.02) at 1.5 and 10 years in patients with diarrhoea WHO grade 3 and 4; 89.5%, 75.9% and 65.1% compared to 83.5%, 49.3% and 44.4% in patients with no or minimal radiation-induced loose bowels. These results indicate that the reaction of the normal bowel to radiation may correlate to radiation sensitivity of tumours derived from the same tissue.

Adult↗
PubMed1993

Evaluation of some properties of a phosphorodithioate oligodeoxyribonucleotide for antisense application.

An all phosphorodithioate oligodeoxyribonucleotide (PS2; 17-mer) complementary to the coding region of the rabbit beta-globin mRNA was compared with the normal (PO2) and phosphorothioate (POS) oligonucleotide of the same size and sequence with respect to physicochemical properties and antisense activity in cell-free systems. The melting temperature (Tm) of the PS2-cDNA duplex was reduced by 17 degrees C relative to the PO2-cDNA duplex, compared to 11 degrees C for the POS-cDNA duplex, suggesting a decreased stability of the duplex with an increasing sulfur substitution. Like the POS-derivative, the PS2 oligonucleotide is quite stable against exonucleases, but these modified oligonucleotides showed different stability towards endonucleases and also towards different sub-cellular fractions of MCF-7 cells. During in vitro protein binding studies, the PS2 oligonucleotide showed similar binding (10-20%) to that of the PO2 oligonucleotide, while the POS oligonucleotide bound 60%. In cell-free translation, the PS2 oligonucleotide produced slightly higher specific translation inhibition of rabbit beta-globin mRNA compared to that of the PO2 oligonucleotide, and this was true only at concentration below 2 mM. The POS-derivative, except at 10 mM concentration, always showed higher translation arrest of the rabbit beta-globin mRNA compared to that of the other two oligonucleotides. The present study suggests that the PS2 oligonucleotide offers very little advantage over the POS oligonucleotide for use as an antisense analog.

Animals↗
PubMed1993

Synthesis of a carboxamide linked T*T dimer and its incorporation in oligonucleotides.

The condensation of 5'-O-protected 3'-O-(2-aminoethyl)thymidine with 1,2-dideoxy-1-thyminyl-beta-D-erythro-pentofuranuronic acid gives a T*T dimer with * representing a 3'-OCH2CH2NHC(O)-4' linkage connecting the two pentofuranosyl moieties. The incorporation of this dimer in oligonucleotide sequences show only moderately lowered Tm values when hybridized with a complementary DNA relative to the unmodified DNA duplex. Consistently, no looped-out or bubble-type structure could be detected in DNA duplexes with an internal T*T module. Moreover, the 5-atom carboxamide linker causes complete stop on DNA polymerization and on exonuclease III degradation.

Base Sequence↗