Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases.

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments.

A Novel, Unbiased Analysis Approach for Investigating Population Dynamics: A Case Study on Calanus finmarchicus and Its Decline in the North Sea.

Marine populations are controlled by a series of drivers, pertaining to both the physical environment and the biological environment (trophic predator-prey interactions). There is heated debate over drivers, especially when trying to understand the causes of major ecosystem events termed regime shifts. In this work, we have researched and developed a novel methodology based on Genetic Programming (GP) for distinguishing which drivers can influence species abundance.

Non-random distribution of instability-associated chromosomal rearrangement breakpoints in human lymphoblastoid cells.

Genomic instability is observed in tumors and in a large fraction of the progeny surviving irradiation. One of the best-characterized phenotypic manifestations of genomic instability is delayed chromosome aberrations. Our working hypothesis for the current study was that if genomic instability is in part attributable to cis mechanisms, we should observe a non-random distribution of chromosomes or sites involved in instability-associated rearrangements, regardless of radiation quality, dose, or trans factor expression.

Chromosome breakpoint distribution of damage induced in peripheral blood lymphocytes by densely ionizing radiation.

Purpose: To assess the chromosomal breakpoint distribution in human peripheral blood lymphocytes (PBL) after exposure to a low dose of high linear energy transfer (LET) alpha-particles using the technique of multiplex fluorescence in situ hybridization (m-FISH).

Materials And Methods: Separated PBL were exposed in G0 to 0.5 Gy 238Pu alpha-particles, stimulated to divide and harvested approximately 48 - 50 hours after exposure.

Carcinogenicity of radon/radon decay product inhalation in rats--effect of dose, dose rate and unattached fraction.

Purpose: The effects of inhalation of radon/radon decay products at different total doses, dose rates and 'unattached' fractions were investigated in a life span study in rats.

Materials And Methods: 1574 rats inhaled radon/radon decay products in a purpose-built recirculating exposure system that provided stable/reproducible exposure conditions. 501 were maintained as controls.

Increased complexity of radiation-induced chromosome aberrations consistent with a mechanism of sequential formation.

Complex chromosome aberrations (any exchange involving three or more breaks in two or more chromosomes) are effectively induced in peripheral blood lymphocytes (PBL) after exposure to low doses (mostly single particles) of densely ionising high-linear energy transfer (LET) alpha-particle radiation. The complexity, when observed by multiplex fluorescence in situ hybridisation (m-FISH), shows that commonly four but up to eight different chromosomes can be involved in each rearrangement. Given the territorial organisation of chromosomes in interphase and that only a very small fraction of the nucleus is irradiated by each alpha-particle traversal, the aim of this study is to address how aberrations of such complexity can be formed.

Intraoperative monitoring during vascular surgery.

The principal objectives of intraoperative monitoring are to improve perioperative outcome, facilitate surgery and reduce adverse events, using continuously collected data of cardiopulmonary,neurologic and metabolic function to guide pharmacologic and physiologic therapy. Although sophisticated and reliable apparatus may be used to collect these data they are useless, or even harmful, without proper interpretation. This article provides a comprehensive overview of recent publications on the history,philosophy, and semantics of monitoring.

In vivo chromosomal instability and transmissible aberrations in the progeny of haemopoietic stem cells induced by high- and low-LET radiations.

Purpose: To study stable and unstable chromosomal aberrations in the haemopoietic cells of CBA/H mice after exposure to both high- and low-LET radiations.

Materials And Methods: Chromosomal aberrations were scored in the clonal progeny of X-, alpha- or non-irradiated short-term repopulating stem cells using the spleen colony-forming unit (CFU-S) assay, 12 days post-transplantation and in the bone marrow reconstituted by X-, neutron- or non-irradiated exogenous (transplanted) or endogenous (X- or neutron whole-body-irradiated) long-term repopulating stem cells for up to 24 months.

Results: Chromosomal instability was demonstrated in 3-6% of cells in all cases.

Susceptibility to radiation-induced leukaemia/lymphoma is genetically separable from sensitivity to radiation-induced genomic instability.

Purpose: To determine whether there is a relationship between the genetics underlying the susceptibility to radiation-induced leukaemia in CBA/H (acute myeloid leukaemia, AML) and C57BL/6 (thymic lymphoma, TL) mice, and the genetics underlying the sensitivity of CBA/H (sensitive) and C57BL/6 (resistant) mice to radiation-induced chromosomal instability.

Materials And Methods: CBA/H, (CBA/H x C57BL/6)F1, F1 x CBA/H, F1 x C57BL/6 and F1 x F1 mice were exposed to a single acute dose of 3.0 Gy X-rays.

Dependence of the yield of DNA double-strand breaks in Chinese hamster V79-4 cells on the photon energy of ultrasoft X rays.

Induction of DNA DSBs by low-LET radiations reflects clustered damage produced predominantly by low-energy, secondary electron "track ends". Cell inactivation and induction of DSBs and their rejoining, assayed using pulsed-field gel electrophoresis, were determined in Chinese hamster V79-4 cells irradiated as a monolayer with characteristic carbon K-shell (CK) (0.28 keV), aluminum K-shell (AlK) (1.

Dose- and time-response relationships for lethal mutations and chromosomal instability induced by ionizing radiation in an immortalized human keratinocyte cell line.

Purpose: To investigate the relationship between two well-established delayed effects of ionizing radiation, experiments were conducted to determine the induction and expression of lethal mutations (delayed reproductive death) and chromosomal instability with respect to dose and time in a human immortalized keratinocyte cell line.

Methods: HPV-G cells were gamma- or alpha-irradiated and maintained in culture for up to 72 population doublings. At intervals, measurements were made of cloning efficiency and the cells examined for apoptosis and cytogenetic aberrations.

Regulation of the apoptotic response to radiation damage in B cell development.

B lymphocyte precursor cells are ultrasensitive to DNA damage induced by irradiation and drugs and die by apoptosis at very low levels of exposure. Previous studies have shown that this high level sensitivity is p53-dependent, associated with very low level expression of Bcl-2 protein and can be reversed by expression of a bcl-2 transgene. We show here that transition from the pro-B to pre-B and then mature B cell stages of murine lymphopoiesis is accompanied by changes in proliferating cells in sensitivity to X-irradiation induced apoptosis and that this is paralleled by variation in the ratio of anti-(Bcl-2/Bcl-chiL) to pro-(Bax) apoptotic proteins.

Imprinting of distal mouse chromosome 2 is associated with phenotypic anomalies in utero.

Previous studies have shown that the distal region on mouse chromosome (Chr) 2 is subject to imprinting as mice with maternal duplication/paternal deficiency (MatDp.dist2) and the reciprocal (PatDp.dist2) for this region exhibit phenotypic anomalies at birth and die neonatally.

X-ray-induced simple, pseudosimple and complex exchanges involving two distinctly painted chromosomes.

Purpose: To detect simple, pseudosimple and complex chromosome exchanges in X-ray-induced aberrations involving two distinctly painted chromosomes. Each visibly complex two-paint exchange was analysed to determine the number of breaks and chromosomes necessary to derive the pattern. In addition, the number of associated paint junctions was scored to assess the frequency of non-reciprocal exchanges.

An investigation of LET 'finger-prints' in Tradescantia.

Chromosome-type aberration scores, obtained in the Tradescantia microspore system following exposure to radiation, have been extracted from all significant papers since 1940, and augmented with unpublished results from this laboratory. The data include aberrations produced by X-, gamma-rays and neutrons, and cover an enormous range of qualities, doses, dose-rates and ambient gas conditions. Two proposed LET 'finger-print' ratios were examined: Dicentrics/Centric-rings (D/R or F-ratio) and Total deletions/Dicentrics+Centric-rings.

Cancer survival in the USA, 1973-1990: a statistical analysis.

Relative survival rates in the National Cancer Institute (NCI) 'SEER' review of cancer in the USA are fitted by a model which can be used to estimate median survival time in any calendar year. It is argued that median survival times (MSTs) are better indicators of survival than 5-year relative survival rates (RSRs), especially when survival times are short.

Investigation of lung tumour induction in C3H/HeH mice, with and without tumour promotion with urethane, following paternal X-irradiation.

In series of papers Nomura has reported that parental irradiation can lead to an enhanced incidence of lung and other tumours. However, in a recent study with BALB/cJ mice, using optimum conditions as defined by Nomura, we were unable to confirm this. We have now repeated the investigation using a different inbred strain, C3H/HeH, with and without tumour promotion in the F1 by urethane, again using protocols defined by Nomura.

Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.

We have investigated the possibility that transgenerational effects from preconceptional paternal irradiation (PPI) may render offspring more vulnerable to secondary exposure to an unrelated carcinogen. 239Pu (0, 128 or 256 Bq g(-1)) was administered by intravenous injection to male mice, 12 weeks before mating with normal females. Two strains of mouse were used -- CBA/H and BDF1.

Effectiveness of 0.28 keV carbon K ultrasoft X-rays at producing simple and complex chromosome exchanges in human fibroblasts in vitro detected using FISH.

Purpose: To study the effects of carbon K ultrasoft X-rays, which produce a single photoelectron with a track length of < 7 nm, on the production of structural chromosome-type changes.

Materials And Methods: Untransformed human fibroblasts (HF12) were irradiated in G1 phase. Aberrations were analysed using fluorescence in situ hybridization using multi-coloured chromosome specific DNA probes for chromosomes 1 and 2 and an alpha-satellite pan-centromeric probe.

Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation.

We have demonstrated chromosomal instability in the clonal descendants of hemopoietic stem cells after irradiating murine bone marrow with alpha-particles. However, because cells that are irradiated by alpha-particles are defined by a Poisson distribution of individual particle traversals, there is an inevitable proportion of unirradiated cells in the surviving population. The calculated expected proportions of irradiated and nonirradiated cells indicate that the number of clonogenic cells transmitting chromosomal instability is greater than the number expected to be hit and survive.

The naevoid basal-cell carcinoma syndrome (Gorlin syndrome) is a chromosomal instability syndrome.

The Gorlin syndrome, or naevoid basal-cell carcinoma syndrome (NBCS) is an autosomal dominant cancer prone disease (at risk of multiple basal cell carcinomas, and other malignant or benign proliferations). We have previously reported data from peripheral blood lymphocytes of patients with this condition, showing a significant level of spontaneous chromatid and chromosome rearrangements and an overall lengthening of the cell cycle. In this paper, we confirm this disease to be a chromosome instability syndrome from studies on fibroblasts of 5 patients.

Abnormalities of copper accumulation in cell lines established from nine different alleles of mottled are the same as those found in Menkes disease.

Menkes disease (MD) is caused by a defect in copper homeostasis and has a recognised mouse model, mottled (Atp7aMo). Copper uptake and retention assays performed on fibroblast cultures have been used successfully for pre- and postnatal diagnosis of Menkes disease. We report here the results of these assays applied to primary fibroblast cultures established from nine independent mottled alleles associated with phenotypes of varying severity maintained on identical genetic backgrounds.

Chromosome 2 hypersensitivity and clonal development in murine radiation acute myeloid leukaemia.

Acute myeloid leukaemias induced by ionizing radiation in mouse are characterized by chromosome (chr) 2 aberrations. While it is known that chr 2 aberrations form early and in abundance post-irradiation, unequivocal evidence for hypersensitivity of chr 2 in the first post-irradiation mitoses is lacking. Here it is established that chromosomal aberrations detected in bone marrow cells by chromosome painting are induced in all mice at an approximately 2-fold greater frequency in chr 2 by comparison with chrs 1 and 3 at 24 and 48 h following in vivo whole-body X-irradiation.