In search of the unknown primary.
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Humans↗
Biomedical subjects
A Rodger
Publications and source records attributed to A Rodger.
The CD of ligand-DNA systems. 2. Poly(dA-dT) B-DNA.
A systematic theoretical study of the CD of [poly(dA-dT)]2 and its complexes with achiral small molecules is presented. The CD spectra of [poly(dA-dT)]2 and of poly(dA):poly(dT) are calculated for various DNA structures using the matrix method. The calculated and experimental spectra agree reasonably well for [poly(dA-dT)]2 but less well for poly(dA):poly(dT). The calculated CD spectrum of [poly(dA-dT)]2 fails to reproduce the wavelength region of 205-245 nm of the experimental spectrum. This discrepancy can be explained by a magnetic dipole allowed transition contributing significantly to the CD spectrum in this region. The induced CD of a transition moment of a molecule bound to [poly(dA-dT)]2 is also calculated. As was the case for [poly(dG-dC)]2, the induced CD of a groove bound molecule is one order of magnitude stronger than that of an intercalated molecule. The calculations also show considerable differences between pyrimidine-purine sites and purine-pyrimidine sites. Both signs and magnitudes of the CD induced into ligands bound in the minor groove agree with experimental observations.
Circular Dichroism↗
Quadrantectomy for early breast cancer.
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Breast↗
Pathological features predictive of local recurrence after management by conservation of invasive breast cancer: importance of non-invasive carcinoma.
The pathological features of 236 clinical stage I and II invasive breast carcinomas treated by conservation were reviewed. On follow-up (minimum 2 years) 13 patients (6%) have developed breast relapse, 10 (4%) regional lymph node relapse and 26 (11%) distant metastases. Nineteen patients have died from breast carcinoma. On univariate analyses lymph node metastases, increasing amounts of non-invasive carcinoma and multiple foci of invasion were significant risk factors for breast relapse. A Cox's multivariate analysis showed the first two of these to be independently significant. The results are in agreement with other published series and confirm that assessment of non-invasive carcinoma is important. The study compares simple quantitation with the original method reported to define cases with an "extensive intraduct component".
Breast Neoplasms↗
A multidisciplinary approach to improving the quality of tangential chest wall and breast irradiation for carcinoma of the breast.
Physicists, radiotherapists and radiographers have worked together to enhance the quality and accuracy of radiotherapy for tangential irradiation of the chest wall and breast. Each stage of the process has been reassessed and improved. A technique has been developed on the treatment simulator which determines the required beam directions and sizes in a straightforward manner. A computerised tomography facility has also been developed on the simulator and this provides one or more slices for planning through the treatment volume, thus allowing accurate determination of external contour and lung position with the patient in the treatment position. The beam edge entry points and the isocentre position can be seen from radiation opaque markers placed on the skin surface, allowing accurate reproduction of the treatment beam positions as set on the simulator. A photon beam algorithm that corrects for the changes in scatter dose in a 3-dimensional (3-D) inhomogeneous situation has been developed and applied to tangential chest wall irradiation. This has shown large differences (up to 10%) in dose compared to a conventional 2-dimensional algorithm. The changes in dose distribution due to the accurate determination of lung position have also been investigated. A method has been developed of measuring the volume of ipsilateral lung irradiated. Dose-area histograms are used to evaluate the fraction of the lung area irradiated in the central slice, and an estimate of the volume irradiated can be made using a beam's eye radiograph and the simulator CT image.
Algorithms↗
Primary radiotherapy for T4 breast cancer.
In Edinburgh in 1982, radiotherapy for patients with T4 breast cancer was modified by an increase in tumour absorbed dose from 42.5-45.0 Gy to 60-75 Gy by using tumour boosts and changing from alternate day to daily fractions. To assess whether this improved local control or survival, the records of all females with T4-N0-3M0 breast cancer referred between January 1978 and December 1985, who received radiotherapy without initial mastectomy or adjuvant chemotherapy, were reviewed. There were 193 patients in the study. Minimum follow-up was 36 months. Actuarial survival at 5 years was 27.1% and median survival 29 months. Local control was achieved by 25.9%. On multivariate analysis, the probability of survival fell with increasing tumour size, advanced clinical node status and the presence of inflammatory change. Radiotherapy technique also affected prognosis. Four-field techniques were associated with a better chance of survival than the breast and axillary jig or other treatment methods. The probability of local control increased with reduced tumour size and showed the same relationship to radiotherapy technique as did survival. Dose was not a significant variable for either survival or local control. No improvement in survival or local control was apparent in comparison with a previous study. It is concluded that radiotherapy alone at a dose of 60 Gy is insufficient to produce durable local control for the majority of women with T4 breast cancer.
Aged↗
The value of internal fixation and radiotherapy in the management of upper and lower limb bone metastases.
Fifty-four consecutive patients underwent 61 orthopaedic operations for metastatic bone disease affecting the upper and lower limbs. These patients were subsequently managed using a consistent postoperative radiotherapy (RT) policy. There were 27 prophylactic internal fixations and 34 internal fixations of pathological fractures. There was a marked difference in survival between these groups. The median postoperative survival of the prophylactic (P) group was 15 months whereas that of the fracture (F) group was 2 months (P less than 0.0001). Ninety-three per cent of the P group and 59% of the F group were able to be discharged home following treatment. Subsequent local fracture requiring further surgical intervention occurred in 11% of the P group and in none of the F group. Seventy-eight per cent of the P group and 62% of the F group did not suffer any further sequelae at the operation site until the time of death or last follow-up. Patient mobility following surgery and RT for metastatic lesions occurring in the lower limb was significantly improved in both the P group (P less than 0.05) and in the F group (P less than 0.0001) such that 91% and 58%, respectively, of these patients were subsequently able to walk.
Adult↗
Locally advanced breast cancer: report of phase II study and subsequent phase III trial.
Twenty-four evaluable patients with stage T4 breast cancer were entered into a phase II study and received chemotherapy comprising cyclophosphamide 1,000 mg m-2 i.v., doxorubicin 50 mg m-2 i.v., vincristine 1.4 mg m-2 i.v. and prednisolone 40 mg orally for 5 days, given 3 weekly for four cycles prior to undergoing loco-regional radiotherapy. All patients completed treatment as planned with no major acute toxicity from either chemotherapy or radiotherapy. Subsequently 52 patients with stage T4 breast cancer were randomised in a phase III trial to receive either radiotherapy alone (RT) or this chemotherapy and radiotherapy (CHOP + RT). A significantly higher complete response rate was achieved in the CHOP + RT treatment arm (P = 0.03). However a larger proportion of the RT arm achieved loco-regional control after salvage treatment for relapse such that 50% of the RT arm and 57% of the CHOP + RT arm had no evidence of loco-regional disease at the time of last follow-up or death. There was no statistical difference in time to distant relapse or overall survival. Analysis of the pilot study showed results comparable to the trial CHOP + RT arm. This trial suggests that this cytotoxic therapy used in conjunction with radiotherapy has only marginal value in improving prognosis in locally advanced breast cancer.
Adult↗
Preliminary results of the use of urinary excretion of pyridinium crosslinks for monitoring metastatic bone disease.
The collagen crosslinks, pyridinoline and deoxypyridinoline, are recently described markers of the rate of bone resorption. The urinary excretion of these compounds, expressed as a ratio to urinary creatinine, has been measured using ion-pair reversed phase high-performance liquid chromatography in 20 patients receiving oral pamidronate for bone metastases from breast cancer. Before treatment the ratio of pyridinoline and deoxypyridinoline to creatinine in urine (UPCR and UdPCR respectively) were each above normal in 16/20 (80%) patients. Urinary calcium excretion (UCCR) was elevated in 15/20 (75%). There was a strong correlation between UPCR and UdPCR, but neither of the crosslink measurements correlated well with UCCR. Urinary excretion of all three indices of bone resorption fell significantly during pamidronate treatment. The median values after 4 weeks treatment were 63% of baseline for UPCR, 45% for UdPCR and 26% for UCCR. From this preliminary study urinary pyridinoline and deoxypyridinoline excretion appear to be promising markers of bone resorption in advanced malignancy. Their role in response assessment and the advantages over UCCR measurements merit further study.
Administration, Oral↗
A molecular dynamics simulation of a polyamine-induced conformational change of DNA. A possible mechanism for the B to Z transition.
A 75ps molecular dynamics simulation has been performed on a fully solvated complex of spermine with the B DNA decamer (dGdC)5.(dGdC)5. The simulation indicates a possible mechanism by which polyamines might induce the formation of a left-handed helix, the B to Z transition. Spermine was initially located in the major groove, hydrogen bonded to the helix. During the simulation the ligand migrates deeper into the DNA, maintaining strong hydrogen bonding to the central guanine bases and destroying the Watson-Crick base pairing with their respective cytosines. Significant rotation of these and other cytosine bases was observed, in part due to interactions of the helix with the aminopropyl chains of spermine. An intermediate BII conformation might be of importance in this process.
Base Sequence↗
Teaching of basic life support.
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Cardiopulmonary Resuscitation↗
Treating bony metastases.
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Bone Neoplasms↗
A molecular mechanics study of spermine complexation to DNA: a new model for spermine-poly(dG-dC) binding.
Molecular mechanics calculations of the binding of spermine to a number of solvated DNA helices have led to the development of a new model for spermine complexation. The structural details of the complexes formed with d(GCGCGCGCGC)2 and d(ATATATATAT)2 decamers allowed a rationalization of the observed experimental differences for binding to these two helices. For d(ATATATATAT)2 it was concluded that spermine remains in a cross-major groove binding site. Conversely, for d(GCGCGCGCGC)2 spermine reorientation via specific ligand-base-pair hydrogen-bond formation allows complexation along the major groove. The solvent plays an important role in differentiating the two binding modes. A mechanism of spermine complexation to natural DNA is postulated from these results. Past experimental data are also considered in the context of the new model.
Base Sequence↗
Side effects expected and experienced by women receiving chemotherapy for breast cancer.
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Adult↗
The CD of ligand-DNA systems. I. Poly(dG-dC) B-DNA.
A systematic theoretical study of the CD of double-stranded poly(dG-dC) and its complexes with small molecules is presented. The intrinsic CD of the polymer and the induced CD of a transition belonging to a molecule bound to DNA are calculated using the matrix method. The calculations show considerable differences between pyrimidine-purine and purine-pyrimidine binding sites, and we find that the induced CD of a groove bound molecule is one order of magnitude stronger than that of an intercalated molecule. The results form a sound basis for interpreting the CD of ligand-DNA systems in terms of molecular geometry, interactions, and spectroscopy.
Circular Dichroism↗
Mitozantrone and prednimustine in the treatment of advanced breast cancer--a toxic regimen with low activity.
The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.
Adult↗
Sequence selective binding to the DNA major groove: tris(1,10-phenanthroline) metal complexes binding to poly(dG-dC) and poly(dA-dT).
Molecular modelling and energy minimisation calculations that incorporate solvent effects have been used to investigate the complexation of delta and lambda-[Ru(1,10-phenanthroline]2+ to DNA. The most stable binding geometry for both enantiomers is one in which a phenanthroline chelate is positioned in the major groove. The chelate is partially inserted between neighbouring base pairs, but is not intercalated. For delta, though not for lambda, a geometry with two chelates in the major groove is only slightly less favourable. Minor groove binding is shown to be no more favourable than external electrostatic binding. The optimised geometries of the DNA/[Ru(1,10-phenanthroline]2+ complexes enable published linear dichroism spectra to be used to determine the percentage of each enantiomer in the two most favourable major groove sites. For delta 57 +/- 15% and for lambda 82 +/- 7% of bound molecules are in the partially inserted site.
Base Sequence↗
A binding mode of lambda-[tris(1,10-phenanthroline)ruthenium(II)]2+ exhibiting preference for purine-3',5'-pyrimidine sites of DNA.
Molecular mechanics calculations and molecular dynamics simulations have been used to study the binding of the partially inserted major groove complex of Lambda-[Ru(1,10-phenanthroline)3]2+ with DNA. Energy refinements of this complex showed a clear preference for binding at purine-3',5'-pyrimidine sites over pyrimidine-3',5'-purine sites. The basis for this difference is shown to be a slight change in the binding orientation induced by interchanging the purine and pyrimidine bases. This in turn provides for a better secondary interaction with the helix backbone at a point beyond the immediate binding site. It is this secondary interaction that provides the additional energetic stabilisation for complexes formed at purine-3',5'-pyrimidine sites. Molecular dynamics simulations including explicit representation of solvent support these conclusions and provide an insight into the positional stability of the ligand at a particular site. Repuckering of specific deoxyribose rings to the C3'-endo conformation seems to be an important feature of the DNA/ligand complex.
Base Sequence↗