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Biomedical subjects

O Mella

Publications and source records attributed to O Mella.

At least 55 records · Page 3Linked to original sources
PubMed1986

Glioma cell interactions with fetal rat brain aggregates in vitro and with brain tissue in vivo.

Two malignant rat neurogenic cell lines have been confronted with reaggregation cultures of fetal rat brain in a stationary culture system. In this organ culture system several morphological aspects of the developing brain are imitated. The malignant cell lines showed invasive and progressive growth into the brain tissue, ending with a completely destroyed aggregate within 10 days of coculture. One cell line (BT5C) showed solid invasion with groups of cells replacing different layers of the brain tissue. A considerable degree of normal cell lysis was seen, both at the edge of invasion and at distant parts of the aggregate. This cell line seemed to activate macrophages in the aggregates. In addition, conditioned medium from these cultures caused degeneration of the brain aggregates. The other cell line (BT4Cn) showed invasion by single cells where the replacement and destruction of the tissue was not accompanied by distant lysis. Both cell lines showed the same pattern of invasion in vitro as was seen in the brains of isogeneic animals in vivo, showing that the individual tumor characteristics were also reflected during invasive growth in organ culture.

Animals↗
PubMed1985

Combined modality treatment of operated astrocytomas grade 3 and 4. A prospective and randomized study of misonidazole and radiotherapy with two different radiation schedules and subsequent CCNU chemotherapy. Stage II of a prospective multicenter trial of the Scandinavian Glioblastoma Study Group.

A prospective and randomized trial has been performed in order to evaluate combined modality therapy in patients with astrocytomas grade 3 and 4. Follow-up information is available on 244 patients. One half of the series received radiation therapy twice a week (40.00 Gy/5 weeks), the other half five times a week (50.00 Gy/5 weeks). Misonidazole 1.2 g/m2 was given orally to one half of the patients in the first radiation treatment group 3 1/2 to 4 hours before the treatment. The other half received placebo. The second radiation treatment group was also divided in two halves, one receiving 0.48 g/m2 misonidazole and the other placebo 3 1/2 to 4 hours before radiation. The randomization also included a subdivision of the material into eight groups of which four were given CCNU and four no chemotherapy, beginning 3 months after operation. The dose of CCNU was 120 mg/m2 body surface every 6 weeks. All eight treatment groups showed practically identical periods of median survival, and no statistically significant differences were observed with regard to performance status, side effects, or complications. Another dosage and timing of misonidazole administration in relation to the irradiation schedule, and a consideration of effects of concomitant drugs like dexamethasone and phenytoin are discussed.

Actuarial Analysis↗
PubMed1984

Radiotherapy and resection for apparently inoperable rectal adenocarcinoma.

Sixty-seven patients with primary, apparently inoperable rectal adenocarcinomas were referred for radiotherapy from a defined geographic region in Norway during the period from 1976 to 1981. Fifty-five were without detectable metastasis at referral and were potentially resectable. Patients were given high energy radiation towards abdominal chimney or pelvic fields to a dose of 3150 rads. Resection was attempted after three weeks. Additional radiotherapy was given to both resected and nonresected patients to a NSD (nominal standard dose) of 1400 to 1560 ret (rad equivalent therapy). At full radiation dose, nonresected patients were reexamined, and in some explorative laparotomy with resection was attempted. Twenty patients had radical resections in the pelvis, but five of them had moderately advanced distant metastasis. Nine patients are disease-free at 12+ to 76+ months. Although the overall prognosis for the patients with apparently inoperable rectal adenocarcinomas remains poor (median survival 12 months), some patients can achieve long-term disease-free survival after combined radiotherapy and surgery. Patients with moderately advanced metastasis can enjoy a better of quality of life without local symptoms following the combined treatment.

Adenocarcinoma↗
PubMed1983

Effect of timing and sequence of hyperthermia and cyclophosphamide on a neurogenic rat tumor (BT4A) in vivo.

The interaction of hyperthermia (HT) 1 hour at 44.0 degrees C and cyclophosphamide (CP) 200 mg/kg was studied in vivo in a solid transplantable neurogenic rat tumor (BT4A) in the foot of BD IX rats. HT was given by water bath heating. When both modalities were close in time (CP immediately before HT or 1 hour before HT), an enhanced effect with complete regression and cure of tumors was seen. This could not be obtained with either modality alone. Extending the interval between treatments within 24 hours, an effect equal to the sum of each modality was obtained when HT was given before CP, while HT after CP was less effective. Timing and sequence may be critical factors for the optimal combination of HT and cytotoxic drugs.

Animals↗
PubMed1982

Chemotherapy of a malignant, metastasizing giant-cell tumor of bone: report of an unusual case and the response to combination chemotherapy.

A 13-year-old girl was treated surgically for a giant-cell tumor of bone originating in the talus and for a recurrence in the distal tibia. She later developed liver and lung metastases and was treated for two years, five months with a combination of vincristine, doxorubicin, cyclophosphamide and actinomycin-D, and thereafter with high-dose methotrexate/vincristine with citrovorum factor rescue. A good response was obtained and the patient is without evidence of disease 12 months after a salvage thoracotomy for residual disease in the left lung. Aspects of this singular case are discussed.

Adolescent↗
PubMedDate not supplied

Referee: hyperthermia alone or combined with cisplatin in addition to radiotherapy for advanced uterine cervical cancer.

There are two evidence based therapeutic options for locally advanced cervical cancer: Radiotherapy and concurrent chemotherapy (cisplatin alone or combined with other drugs) or radiation and hyperthermia, documented in randomised trials. The weight of evidence is less for the most advanced stages. Combination of all three options are currently tested in several centres with good clinical response and acceptable toxicity. Based on a pragmatic approach we propose to proceed with a trial selecting cisplatin concurrent with radiation therapy as the standard arm to be compared with the same regimen with the addition of hyperthermia once a week.

Antineoplastic Agents↗
PubMedDate not supplied

Combined hyperthermia and cis-diamminedichloroplatinum in BD IX rats with transplanted BT4A tumours.

Effects on tumours and toxicity of locally applied waterbath hyperthermia (44 degrees C, 60 min) and cis-diamminedichloroplatinum (cis-DDP) were investigated in BD IX rats with transplanted BT4A tumours on the hind foot. The effect of cis-DDP at doses of 2, 3 and 4 mg/kg measured as tumour growth time, defined as time to reach five times the tumour volume at treatment, increased in a drug dose-dependent manner by using hyperthermia. Moderate systemic hyperthermia at a mean of 41 degrees C during the second half of the treatment also increased the tumour regrowth delay of cis-DDP. Skin reactions after local hyperthermia did not increase in this cis-DDP dose range, but systemic toxicity of the drug was markedly enhanced by hyperthermia. At histological evaluation, hyperthermia at 44 degrees C resulted in marked vasodilatation, red blood cell pooling and haemolysis, with a seemingly almost complete central tumour perfusion shutdown lasting up to five days after treatment. The combination of cis-DDP and hyperthermia resulted in additional cell death especially at the tumour periphery and at depth near the tendon and muscle. This in vivo study confirms in vitro data indicating cis-DDP as a candidate for clinical trials combined with hyperthermia. As both the tumour and systemic side effects of cis-DDP are enhanced by hyperthermia, caution is advocated when applying high drug doses with systemic hyperthermia.

Animals↗
PubMedDate not supplied

Potentiation of combined BCNU and hyperthermia by pH reduction in vitro and hypertonic glucose in vivo in the BT4 rat glioma.

In vitro studies have shown enhanced cell killing of BCNU and hyperthermia at acutely lowered pH. In animals hypertonic glucose i.p. has repeatedly been demonstrated to reduce intratumoral pH. Effect of hyperthermia (43 degrees C for 45 min), or BCNU (3.33 micrograms/ml or both on BT4C cells were investigated in vitro, with pH 7.5, 7.0 and 6.5 in the medium during treatment. The effect of elevated glucose concentration in the medium (20 mmol/l) during treatment with hyperthermia, or BCNU, or both, was also investigated at pH 7.5. BD IX rats with transplanted BT4A or BT4An tumours on the hind foot were treated with BCNU i.p., locally applied water bath hyperthermia (44 degrees C for 45 min) or both, with or without previous glucose (6 g/kg i.p. 2 h before treatment). In vitro: low pH markedly increased cell killing by combined BCNU and hyperthermia, but pH had only a minor influence on treatment with BCNU or hyperthermia alone. Increased glucose concentration in the medium did not influence the effect of BCNU alone, hyperthermia alone, or BCNU and hyperthermia. In vivo: glucose reduced the effect of BCNU alone on BT4A tumours, but did not influence the treatment results with hyperthermia alone. However, glucose enhanced the effect of combined BCNU and hyperthermias. The effect on BT4An tumours of BCNU or hyperthermia alone were not affected by glucose, but glucose markedly enhanced the tumour effect of combined BCNU and hyperthermia. Hyperglycaemia seems to be a promising method to increase the benefit of combined hyperthermia and BCNU. However, glucose-induced altered tumour circulation could hamper the potential benefit by decreased drug uptake.

Animals↗
PubMedDate not supplied

Fractionated hyperthermia in vivo: thermotolerance, sensitivity to BCNU and thermochemosensitivity in the BT4An rat glioma.

Although hyperthermia has been shown to increase the effect of some cytotoxic drugs both in vitro and in vivo, there is sparse data on the interaction of the two modalities during fractionated treatment in vivo. In vitro data suggest that, parallel to development of thermotolerance, tumour cell sensitivity to drugs may be modified. Thermotolerance in tumour and surrounding normal tissue and the sensitivity to the alkylating agent BCNU given alone i.p., or as thermochemotherapy, was investigated in the subcutaneously transplanted BT4An rat glioma. Tumours treated by 44 degrees C water bath hyperthermia alone minutes after the priming hyperthermia were initially sensitive to hyperthermia, but decreased heat sensitivity developed during continued heating. Thermotolerance in the skin was greatest at 24 h. When the skin reaction was compared with the effect on tumours, a therapeutic gain using hyperthermia alone was seen at 168 h. Tumours were most sensitive to BCNU just after the priming hyperthermia, least sensitive at 48 h. When thermochemotherapy with BCNU was given at different intervals after priming hyperthermia, an interaction between the modalities was seen, with the greatest tumour effect just after priming (six of 12 tumours controlled). At 24 h the summary effect of priming treatment and subsequent thermochemotherapy was not greater than thermochemotherapy treatment alone. The thermochemotherapy effect on tumours was more dependent on the hyperthermia sensitivity, i.e. thermotolerant state, than the sensitivity to BCNU alone at that time.

Animals↗
PubMedDate not supplied

Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology.

The ESHO protocol 3-85 is a multicentre randomized trial investigating the value of hyperthermia as an adjuvant to radiotherapy in treatment of malignant melanoma. A total of 134 metastatic of recurrent malignant melanoma lesions in 70 patients were randomized to receive radiotherapy alone (3 fractions in 8 days) or each fraction followed by hyperthermia (aimed for 43 degrees C for 60 min). Radiation was given with high voltage photons or electrons. Tumours were stratified according to institution and size (above or below 4 cm) and randomly assigned to a total radiation dose of either 24 or 27 Gy to be given with or without hyperthermia. The endpoint was persistent complete response in the treated area. A number of 128 tumours in 68 patients were evaluable, with an observation time between 3 and 72 months. Sixty-five tumours were randomized to radiation alone and 63 to radiation + heat. Sixty received 24 Gy and 68 tumours received 27 Gy, respectively. Size was < or = 4 cm in 81 and > 4 cm in 47 tumours. Overall the 2-year actuarial local tumour control was 37%. Univariate analysis showed prognostic influence of hyperthermia (rad alone 28% versus rad + heat 46%, p = 0.008) and radiation dose (24 Gy 25% versus 27 Gy 56%, p = 0.02), but not of tumour size (small 42% versus large 29%, p = 0.21). A Cox multivariate regression analysis showed the most important prognostic parameters to be: hyperthermia (odds ratio: 1.73 (1.07-2.78), p = 0.02), tumour size (odds ratio: 0.91 (0.85-0.99), p = 0.05) and radiation dose (odds ratio: 1.17 (1.01-1.36), p = 0.05). Analysis of the heating quality showed a significant relationship between the extent of heating and local tumour response. Addition of heat did not significantly increase the acute or late radiation reactions. The overall 5-year survival rate of the patients was 19%, but 38% in patients if all known disease was controlled, compared to 8% in the patients with persistent active disease.

Adult↗
PubMedDate not supplied

Effect of hypertonic glucose in thermotolerant rat BT4An gliomas treated with combined hyperthermia and BCNU in vivo.

The influence of hypertonic glucose i.p. on development of thermotolerance and thermochemosensitivity with BCNU in thermotolerant tumours, and on intratumoural pH alterations in previously unheated and thermotolerant tumours, was investigated in BT4An tumours grown on the hind foot of BD IX rats. Thermotolerance was induced with local waterbath hyperthermia (44 degrees C/45 min) 24 h before start of test treatment. Hypertonic glucose immediately after priming hyperthermia did not inhibit development of thermotolerance, despite a significant reduction of pH by glucose. The pH reduction was less in thermotolerant tumours. Glucose administered before treatment of thermotolerant tumours did not change the growth rate of tumours treated with hyperthermia (44 degrees C/45 min), BCNU (20 or 25 mg/kg i.p.) or thermochemotherapy with a low or high dose BCNU (10 or 20 mg/kg), in contrast to previous results, where glucose enhanced thermochemosensitivity of non-thermotolerant tumours.

Animals↗
PubMedDate not supplied

Quality assurance for radiofrequency regional hyperthermia.

Today most treatments with regional hyperthermia are applied using radiofrequency systems with 'focus' steering by amplitude and phase control. This paper deals with quality assurance procedures developed to ensure controlled and safe treatments in such systems. Our results show how the deviations between requested and observed phase and amplitude vary with frequency, and how these deviations depend on both the geometry of the object (phantom) inside the system and the power level applied. The results also indicate that the investigated systems' internal quality assurance procedures were inadequate and that additional procedures should be applied. Since the system parameters depend on patient and treatment specific conditions it is concluded that there is a need for QA measurements before or during treatment. This paper deals specifically with the commercial BSD-2000 system from BSD Medical Corp. in Salt Lake City, Utah, as installed in Bergen, but the procedure outlined can be applied to other phase and amplitude-controlled RF-RHT systems with only minimal adjustments.

Calibration↗
PubMedDate not supplied

Intravenous infusion of glucose and the vasodilator sodium nitroprusside in combination with local hyperthermia: effects on tumour pH and tumour response in the BT4An rat tumour model.

The influence of sodium nitroprusside (SNP) induced hypotension on the extra-cellular tumour pH during local hyperthermia (HT), and on the cytotoxic effect of HT, was studied in the BT4An tumour transplanted to the hind limb of BD IX rats. Experiments with intravenous infusion of glucose before the HT/SNP combination were also performed. Local waterbath HT was given at 44 degrees C. Sodium nitroprusside was administered as a continuous i.v. infusion to lower the mean arterial blood pressure to 60 mmHg. Glucose was given as an i.v. infusion at a dosage of 4.8 g/kg body weight in 60 min before HT. Extracellular tumour pH was measured by a needle type glass electrode. The tumour pH fell from 7.19 to 6.81, on average, after 60 min HT. Sodium nitroprusside induced hypotension during HT did not increase the pH fall after 1 h HT, but the pH 60 min after discontinuation of HT was lower in this group than in the HT alone group. Pretreatment with glucose before HT gave similar results as the HT/SNP combination. When glucose was given before HT/SNP a highly relevant decline in tumour pH during HT from 7.22 to 5.95 was observed. In a separate tumour response experiment adding SNP to HT was found to prolong the tumour growth time. Pre-treatment with glucose before the HT/SNP combination prolonged the tumour growth time slightly. The applicability of this treatment protocol in the clinical treatment of patients is discussed.

Animals↗
PubMedDate not supplied

Hyperthermia or BCNU alone and combined in BD IX rats with BT4An tumours. Effects of a single or two equal fractions at different intervals.

BD IX rats with BT4An tumours subcutaneously on the hind leg were stratified after tumour size and treated by single dose 44 degrees C water bath hyperthermia for 90 minutes or with two 45 minute sessions at 24, 48 or 168 hour intervals. Other groups were treated by single dose BCNU at 20 mg/kg or by two divided doses at the same intervals, or by combined hyperthermia and drug as single treatment or as divided treatments at the same intervals. Intratumoural temperatures in some animals were carefully scanned for minimal temperature during two hyperthermia sessions 24 hours apart. Tumour response, normal skin damage and weight was evaluated. It was concluded that single dose hyperthermia and combined treatment yielded the best effect, but also resulted in the most severe skin reaction and weight loss. Hyperthermia was least effective at a 24 hour interval, indicating thermotolerance to be greatest at this time. The minimum intratumoural temperatures were higher at the second heat dose given at 24 hours, demonstrating a poorer ability to dissipate heat after the first treatment. The tumours were only slightly sensitive to BCNU alone, and no optimal schedule was found. BCNU increased the hyperthermia effect at all schedules, except for the 168 hour interval. The skin reaction to single dose hyperthermia was enhanced by BCNU.

Animals↗
PubMedDate not supplied

Timing of combined hyperthermia and 1,3-bis(2-chloroethyl)-1-nitrosourea or cis-diamminedichloroplatinum in BD IX rats with BT4A tumours.

Groups of 7-10 evaluable BD IX rats with the neurogenic BT4A tumour on the right hind leg were treated with waterbath hyperthermia (44 degrees C, 60 min) in combination with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) 20 mg/kg or cis-diamminedichloroplatinum (cis-DDP) 3 mg/kg i.p. at different sequences and timing within +/- 24 hr. Tumour responses were evaluated by tumour doubling time and clinical criteria, toxicity by toxic deaths, weight loss, and local skin reactions. With both BCNU and cis-DDP, tumour response was markedly dependent on timing; the greatest effects were obtained giving hyperthermia just after the drug. Local side effects were not different in the timing groups, but cis-DDP general toxicity was most severe when cis-DDP was given just before hyperthermia.

Animals↗