Differential cell death response to photodynamic therapy is dependent on dose and cell type

PDT-induced cell death, by either apoptosis or necrosis may vary with cell type or PDT dose. 5 cell types were treated with varying doses of aminolaevulinic acid-induced PDT and the type of cell death analysed. The mode of cell death was found to depend on both cell type and light dose. © 2001 Cancer Research Campaign www.bjcancer.co

Lipid droplet detection by the cavity perturbation method

There are currently no point-of-care diagnosis strategies available to indicate the presence of neoplasmic growth. This research aims to develop a novel diagnostic strategy based on detecting TAG accumulation in cells. This element of the research is a preliminary experiment to prove the concept of detecting TAG lipid droplets in YEPD media. It was found that a change in mono-unsaturated concentration can be detected by the frequency shift in a resonant cavity. The dielectric constant of TAG vegetable oils was calculated at 2.34-2.39. It was also found that concentrations of lipid droplet can be differentiated up to 5% (v/v)

Aminolaevulinic acid-induced photodynamic therapy: cellular responses to glucose starvation

Photodynamic therapy is a cancer treatment based on the interaction of light, oxygen and a photosensitiser. Protoporphyrin. IX is an endogenous photosensitiser derived from the pro-drug aminolaevulinic acid. Tumours contain areas of hypoxia and hypoglycaemia. Tumour cells adapt to these conditions by stress protein induction which may induce resistance to cancer therapies. The effect of chronic hypoglycaemia on sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro was studied in MCF-7, human breast cancer cells. Following chronic exposure to 0, 1 or 25 mM, glucose, cells were treated with aminolaevulinic acid and the generation of intracellular protoporphyrin. IX measured by spectrofluorimetry. Aminolaevulinic acid-induced photodynamic therapy sensitivity was compared between cells following chronic exposure to 0, 1 or 25 mM glucose. Percentage cell survival was determined by clonogenic assay. Cells cultured in low glucose generated higher levels of protoporphyrin IX compared to standard glucose medium (0 mM glucose: 0.88×10−5 ng cell−1, 1 mM: 0.86×10−5 ng cell−1, 25 mM: 0.605×10−5 ng cell−1, P<0.05). However, photodynamic therapy sensitivity was reduced in glucose deprived cells (0 mM glucose: 61% survival, 1 mM: 80.5% and 25 mM: 39.6%, P<0.05). Chronic exposure to low glucose induces photodynamic therapy resistance despite increased intracellular concentrations of protoporphyrin IX and may reflect cellular adaptation to chronic glucose deprivation

Healthcare professionals' preferences for surgery or primary endocrine therapy to treat older women with operable breast cancer

Introduction : Primary endocrine therapy (PET) is an alternative treatment to surgery for oestrogen receptor (ER) positive operable breast cancer in older women. However, there is variable use of PET in the UK, with up to 40% of patients aged over 70 receiving PET instead of surgery in some regions. Treatment options offered to patients rely heavily on healthcare professional (HCP) assessment and opinion on which treatments are appropriate. Materials and methods : This was a mixed methods study combining semi-structured interviews with HCPs working in high and low PET regions in the UK, followed by a postal questionnaire survey distributed via the Association of Breast Surgery (ABS). Results : Thirty-four HCPs (20 breast surgeons; 13 nurse specialists; 1 geriatrician) were interviewed from 14 sites across the UK and 252/641 questionnaires returned (39%). There was an overriding view that PET is not suitable for patients under the age of 80 unless there are significant comorbidities. Opinion was split regarding the best way to treat patients with dementia. Patient preference was generally stated to be the most important factor when considering treatment, however only around a quarter 65/244 (26.6%) felt that all patients over the age of 70 should be offered PET as an alternative treatment option. Conclusions : Opinions differ on the best way to treat women over 70 with operable breast cancer, especially if they have co-existing dementia, as well as whether they should be offered PET as a treatment option. This may be a significant cause of treatment variation in the UK. Keywords : Breast cancer; Primary endocrine therapy; Surgery; Elderly; Older; Mixed methods.</p

Equation of the field lines of an axisymmetric multipole with a source surface

Optical spectropolarimeters can be used to produce maps of the surface magnetic fields of stars and hence to determine how stellar magnetic fields vary with stellar mass, rotation rate, and evolutionary stage. In particular, we now can map the surface magnetic fields of forming solar-like stars, which are still contracting under gravity and are surrounded by a disk of gas and dust. Their large scale magnetic fields are almost dipolar on some stars, and there is evidence for many higher order multipole field components on other stars. The availability of new data has renewed interest in incorporating multipolar magnetic fields into models of stellar magnetospheres. I describe the basic properties of axial multipoles of arbitrary degree ℓ and derive the equation of the field lines in spherical coordinates. The spherical magnetic field components that describe the global stellar field topology are obtained analytically assuming that currents can be neglected in the region exterior to the star, and interior to some fixed spherical equipotential surface. The field components follow from the solution of Laplace’s equation for the magnetostatic potential

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p=0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p=0.04 and p<0.005

What influences healthcare professionals' treatment preferences for older women with operable breast cancer?: an application of the discrete choice experiment

Introduction Primary endocrine therapy (PET) is used variably in the UK as an alternative to surgery for older women with operable breast cancer. Guidelines state that only patients with “significant comorbidity” or “reduced life expectancy” should be treated this way and age should not be a factor. Methods A Discrete Choice Experiment (DCE) was used to determine the impact of key variables (patient age, comorbidity, cognition, functional status, cancer stage, cancer biology) on healthcare professionals' (HCP) treatment preferences for operable breast cancer among older women. Multinomial logistic regression was used to identify associations. Results 40% (258/641) of questionnaires were returned. Five variables (age, co-morbidity, cognition, functional status and cancer size) independently demonstrated a significant association with treatment preference (p < 0.05). Functional status was omitted from the multivariable model due to collinearity, with all other variables correlating with a preference for operative treatment over no preference (p < 0.05). Only co-morbidity, cognition and cancer size correlated with a preference for PET over no preference (p < 0.05). Conclusion The majority of respondents selected treatment in accordance with current guidelines, however in some scenarios, opinion was divided, and age did appear to be an independent factor that HCPs considered when making a treatment decision in this population

Dispersion Coefficients by a Field-Theoretic Renormalization of Fluid Mechanics

We consider subtle correlations in the scattering of fluid by randomly placed obstacles, which have been suggested to lead to a diverging dispersion coefficient at long times for high Peclet numbers, in contrast to finite mean-field predictions. We develop a new master equation description of the fluid mechanics that incorporates the physically relevant fluctuations, and we treat those fluctuations by a renormalization group procedure. We find a finite dispersion coefficient at low volume fraction of disorder and high Peclet numbers.Comment: 4 pages, 1 figure; to appear in Phys. Rev. Let

Defect generation and deconfinement on corrugated topographies

We investigate topography-driven generation of defects in liquid crystals films coating frozen surfaces of spatially varying Gaussian curvature whose topology does not automatically require defects in the ground state. We study in particular disclination-unbinding transitions with increasing aspect ratio for a surface shaped as a Gaussian bump with an hexatic phase draped over it. The instability of a smooth ground state texture to the generation of a single defect is also discussed. Free boundary conditions for a single bump are considered as well as periodic arrays of bumps. Finally, we argue that defects on a bump encircled by an aligning wall undergo sharp deconfinement transitions as the aspect ratio of the surface is lowered.Comment: 24 page