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Biomedical subjects

O Dahl

Publications and source records attributed to O Dahl.

At least 37 records · Page 2Linked to original sources
PubMed2000

ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Co-operative group of radiotherapy of the european organization for research and treatment of cancer (EORTC).

BACKGROUND: Since there is increasing evidence that both acute (perfusion-limited) and chronic (diffusion-limited) hypoxia, and tumor repopulation may prejudice the outcome of radiotherapy, the combination of carbogen (95% oxygen-5% carbon dioxide) and nicotinamide with accelerated radiotherapy (ARCON) should reduce the impact of these factors of radioresistance. AIM: This clinical study was aimed at determining the feasibility, as well as the qualitative and quantitative toxic effects of a therapeutic approach based on ARCON, and assessing the tumor response rates that can be achieved with this regime in patients with locally advanced tumors of the head and neck. METHODS: A phase I/II study conducted between 1993 and 1996 by the Co-operative Group of Radiotherapy of the EORTC included three consecutive steps: accelerated fractionation (AF) combined with carbogen (11 analyzable patients), AF combined with the daily administration of nicotinamide (n=10), and AF with both carbogen and nicotinamide (n=17). Radiotherapy was based on an accelerated regime (72 Gy in 5.5 weeks). Nicotinamide was delivered 90 min before the first irradiation session, at a daily dose of 6 g. Carbogen breathing started 5 min before irradiation and lasted throughout the entire radiotherapy sessions. RESULTS: No significant difference in loco-regional toxicity was found among the three study steps, when carbogen and nicotinamide, either alone or in combination, were combined with AF. The feasibility of the ARCON protocol, as proposed in the present EORTC study, appears to be significantly impaired when nicotinamide is added, at a daily dose of 6 g, to AF and carbogen, in an unselected group of patients. More than 20% of patients experienced grade 2 or 3 emesis. It also demonstrates, in unselected groups of patients, no significant difference in tumor response and local control when carbogen and nicotinamide, either alone or in combination, are added to accelerated radiotherapy. The percentages of objective response at 2 months were 81, 70 and 87%, respectively. CONCLUSION: Future ARCON trials should target selected head and neck tumor localizations and stages, and a lower nicotinamide dose is needed to reduce severe upper gastro-intestinal toxicity.

Adult↗
PubMed2000

Adapting the waterproof BMS-96 diode array for isodose determination of dynamic beams.

We report the application of the Schuster BMS-96 waterproof linear diode array for isodose determination of dynamic beams. The array recorded beam profiles correctly, while depth dose distributions of dynamic beams with large variations in dose rate were registered erroneously. The deviations could be eliminated by appropriate software modifications. Until the software is revised, true isodoses can be obtained by rescaling each individual profile to the depth dose curve as measured with a single ionization chamber. After the corrections presented in the paper, isodoses interpolated from these corrected data sets agreed with ionization chamber measurements within 1-2%.

Radiation Dosage↗
PubMed2000

Dose-volume analysis of different stereotactic radiotherapy mono-isocentric techniques.

Several stereotactic irradiation techniques, using Linacs with the patient in lying and sitting position and a Gamma Knife Unit, were compared with regard to mono-isocentric three-dimensional dose distributions. Three types of target volumes, a sphere and two ellipsoids, were used for the comparisons. All three targets were centered on a real head, reconstructed from transversal CT scans. The ARTEMIS 3D Treatment Planning System, developed by the Tenon Hospital, Paris, was used for the dosimetry and the dose-volume histogram (DVH) calculation. For the comparative study, several quantitative parameters were used, derived from the dose-volume histogram calculation. Differential DVHs were plotted for each target volume and beam arrangement. Irradiation techniques were compared by deriving quantitative parameters from the DVHs such as mean and integral dose delivered to the target and normal tissue irradiated, as well as by the relative volume of the examined areas. All techniques used in this study produced very similar dose distributions. The small differences confirm the capability of the studied techniques to produce the same irradiation effects. By changing from the spherical target shape to a more elliptical shape, more of the normal tissue was irradiated with higher doses. For elliptical cases we therefore identified a need for more conformal stereotactic planning.

Brain Neoplasms↗
PubMed2000

Partially wedged radiation beams.

To increase dose homogeneity within certain radiotherapy targets, we defined a partially wedged radiation beam as a beam with wedge modification in one part of the field only. Partially wedged beams may be beneficial in cases with curved surfaces inside parts of the beam only, where they may compensate for missing tissue and/or for variations in depth to the target region. Possible sites suitable for partially wedged beams include urinary bladder and tangential breast irradiation. Customized partially wedged beams were delivered applying dynamic collimation techniques. Two different linear detector arrays, a semiconductor diode array and an ionization chamber array, were used independently in the same standard water tank to verify that the partially wedged beams were delivered according to the definition. Dose calculations of partial wedge fields were implemented in our treatment planning system and compared with the measured dose distributions. We re-planned a representative treatment plan for both advanced urinary bladder cancer and tangential breast irradiation using partially wedged beams. For both patients the target dose homogeneity was improved, and the doses to surrounding critical normal tissues were reduced.

Algorithms↗
PubMed1999

Double duplex invasion by peptide nucleic acid: a general principle for sequence-specific targeting of double-stranded DNA.

Pseudocomplementary PNAs containing diaminopurine.thiouracil base pairs have been prepared and are shown to bind with high specificity and efficiency to complementary targets in double-stranded DNA by a mechanism termed "double duplex invasion" in which the duplex is unwound and both DNA strands are targeted simultaneously, each by one of the two pseudocomplementary peptide nucleic acids (PNAs). On the basis of our results we predict that (for decameric targets) more than 80% of all sequences can be targeted by straightforward Watson-Crick base pairing by using this approach in its present form. Targeting of pseudocomplementary PNAs to the promoter of the T7 phage RNA polymerase effectively inhibits transcription initiation. These results have important implications in the development of gene therapeutic agents as well as for genetic diagnostic and molecular biology applications.

Adenine↗
PubMed1999

ARCON: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC.

BACKGROUND: Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours. AIM: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours. METHODS: The phase I/II study included three steps: accelerated fractionation (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11 ) and AF with both carbon and nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy. RESULTS: The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10%, neither in the lung parenchyma nor in the mediastinum. No significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps, of the 25 patients entered in the two Nicotinamide containing steps 10 (40%) developed grade 2 or greater reactions which significantly detracted from their quality of life. There was no significant difference in tumour clearance rate among the three steps. The percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively. CONCLUSION: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant difference in time to progression among the three study steps.

Administration, Inhalation↗
PubMed1999

Tissue prostate-specific antigen and androgen receptor immunoreactivity in prostate cancer biopsies before, during and after neo-adjuvant androgen deprivation followed by radiotherapy.

OBJECTIVE: The purpose of the study was to examine the immunohistochemical stainability of prostate-specific antigen (PSA) and androgen receptor (AR) in biopsies from localised prostate cancers before treatment, after androgen deprivation and after radiation therapy. PATIENTS AND METHODS: Biopsies were taken from 16 men with prostate cancer (T1-3,Nx,M0) before the start (START) of androgen deprivation with LHRH analogue, during the following pelvic lymph node dissection (PLND), and twice after radiotherapy (POSTRAD and FINAL). RESULTS: Malignant cells were observed in all START, PLND and POSTRAD biopsies and in 6 of 7 FINAL specimens. During androgen suppression and subsequent radiotherapy a gradual reduction in tissue immunoreactivity for PSA and AR was observed paralleled by a reduction in serum PSA. The most striking observation was the complete lack of AR stainability after combined LHRH/radiation therapy. Of the 7 patients who had a long-term follow-up after radiotherapy, 1 patient was cancer negative on biopsy and without AR and PSA stainability. Six patients with cancer-positive FINAL biopsies had regained AR stainability. Five of these latter biopsies also stained for PSA. Five of the six patients had no elevation in serum PSA. CONCLUSION: After combined hormone/radiotherapy serum PSA is a relatively unreliable marker for the demonstration of residual cancer. This combination therapy leads to transient loss of immunohistochemically stained tissue PSA and AR in the residual cancer.

Aged↗
PubMed1998

Recognition of single-stranded DNA by nuclease P1: high resolution crystal structures of complexes with substrate analogs.

The reaction mechanism of nuclease P1 from Penicillium citrinum has been investigated using single-stranded dithiophosphorylated di-, tetra-, and hexanucleotides as substrate analogs. The complexes crystallize in tetragonal and orthorhombic space groups and have been solved by molecular replacement. The high resolution structures give a clear picture of base recognition by P1 nuclease at its two nucleotide-binding sites, especially the 1.8 A structure of a P1-tetranucleotide complex which can be considered a P1-product complex. The observed binding modes are in agreement with a catalytic mechanism where the two closely spaced zinc ions activate the attacking water while the third, more exposed zinc ion stabilizes the leaving 03' oxyanion. Stacking as well as hydrogen bonding interactions with the base 5' to the cleaved phosphodiester bond are important elements of substrate binding and recognition. Modelling of a productive P1-substrate complex based on the solved structures suggests steric hindrance as the likely reason for the resistance of Rp-phosphorothioates and phosphorodithioates. Differences with the highly homologous nuclease S1 from Aspergillus oryzae are discussed.

Catalysis↗
PubMed1998

Synthesis and hybridization properties of an acyclic achiral phosphonate DNA analogue.

Protected N-(2-hydroxyethyl)-N-(nucleobase-acetyl)aminomethanephosphonic+ ++ acid (6a-d) of all four DNA nucleobases have been prepared and oligomerized by solid-phase synthesis. Four DNA decamers containing 1-10 of these 'PPNA' monomers were prepared and evaluated by Tm measurements (medium salt) for binding to their DNA and RNA complements. One central modification reduced the binding strongly (delta Tm = -10 degrees C), but contiguous PPNA monomers gave smaller effects, and the all-PPNA decamer bound to RNA with a delta Tm of -1.2 degrees C per modification. Thus PPNA oligomers are inferior DNA and RNA binders compared to the closely related and strongly binding PNA oligomers.

DNA↗
PubMed1997

Increased DNA binding and sequence discrimination of PNA oligomers containing 2,6-diaminopurine.

The synthesis of a diaminopurine PNA monomer, N-[N6-(benzyloxycarbonyl)-2,6-diaminopurine-9-yl] acetyl-N-(2-t-butyloxycarbonylaminoethyl)glycine, and the incorporation of this monomer into PNA oligomers are described. Substitution of adenine by diaminopurine in PNA oligomers increased the T m of duplexes formed with complementary DNA, RNA or PNA by 2.5-6.5 degrees C per diaminopurine. Furthermore, discrimination against mismatches facing the diaminopurine in the hybridizing oligomer is improved. Finally, a homopurine decamer PNA containing six diaminopurines is shown to form a (gel shift) stable strand displacement complex with a target in a 246 bp double-stranded DNA fragment.

2-Aminopurine↗
PubMed1997

Quality assurance in conformal radiotherapy: DYNARAD consensus report on practice guidelines.

BACKGROUND AND PURPOSE: Conformal radiotherapy has only recently been widely implemented. Although not all aspects have yet been adequately proven, it is generally recognized that maintaining a high degree of precision throughout the process is critical to the treatment outcome while the focus for quality assurance and quality improvement will need to concentrate more on human factors, procedures, communication, organization and training. A general consensus document on quality assurance guidelines for institutions that deliver conformal radiotherapy treatments to patients has been elaborated within the framework of the DYNARAD/BIOMED concerted action on conformal radiotherapy. The present paper aims to highlight those issues that were identified as of specific importance to conformal radiotherapy. The work reported here further details this guidance by direct correlation with the issues involved in the special case of conformal radiotherapy. METHODS: The DYNARAD document has been drafted in the form of a desktop guide comprising six sets of guidelines and is based on the ESTRO advisory report on 'Quality Assurance in Radiotherapy'. RESULTS AND CONCLUSIONS: The document has been endorsed by the DYNARAD group of institutions. As such it can form the basis for further discussions and enter into the subsequent phase of expanding its consensus basis.

Consensus Statements as Topic↗
PubMed1997

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer.

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

Biomarkers, Tumor↗