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

Cell cycle phase influences tumour cell sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro.

Photodynamic therapy (PDT) is a form of cancer treatment based on the destruction of cells by the interaction of light, oxygen and a photosensitizer. Aminolaevulinic acid (ALA) is the prodrug of the photosensitizer protoporphyrin IX (PpIX). ALA-induced PDT depends on the rate of cellular synthesis of PpIX, which may vary with cell cycle phase. This study has investigated the relationship between cell cycle phase, PpIX generation and phototoxicity in synchronized and unsynchronized bladder cancer cells (HT1197). In unsynchronized cells, relative PpIX fluorescence values (arbitrary units) were significantly different between cell cycle phases after a 1-h ALA incubation (G1 24.8 +/- 0.7; S-phase, 32.7 +/- 0.8, P < 0.05; G2 35.4 +/- 0.8, P < 0.05). In synchronized cells after a 1-h ALA incubation, cells in G1 produced less PpIX than those in S-phase or G2 [6.65 +/- 1.1 ng per 10(5) cells compared with 15.5 +/- 2.1 (P < 0.05), and 8.1 +/- 1.8 ng per 10(5) cells (not significant) respectively] and were significantly less sensitive to ALA-induced PDT (% survival, G1 76.2 +/- 8.3; S-phase 49.7 +/- 4.6, P < 0.05; G2 44.2 +/- 2.4, P < 0.05). This differential response in tumour cells may have implications for clinical PDT, resulting in treatment resistance and possible failure in complete tumour response

Langevin equation with scale-dependent noise

A new wavelet based technique for the perturbative solution of the Langevin equation is proposed. It is shown that for the random force acting in a limited band of scales the proposed method directly leads to a finite result with no renormalization required. The one-loop contribution to the Kardar-Parisi-Zhang equation Green function for the interface growth is calculated as an example.Comment: LaTeX, 5 page

Special issues for older women with primary breast cancer

It is estimated that the number of older women living with breast cancer will quadruple by 2040 [1]. Despite this, there is a lack of strong evidence and guidelines to support management decisions for this population. This article has evolved from a conference session on this subject, held at the 2020 UK Interdisciplinary Breast Cancer Symposium (UKIBCS; West Midlands, UK, 27–28 January 2020) [2]. The UKIBCS is a biennial meeting for all those with an active interest in breast cancer research and treatment, hosted by the charity Breast Cancer Now (London, UK), in collaboration with eight other breast cancer focused specialist societies. In this editorial, we discuss key issues in the management of breast cancer in older women, which include both tumor and patient factors. We also review current national initiatives to tackle these issues and summarize ongoing work in this field

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

The views of older women towards mammographic screening: a qualitative and quantitative study

Purpose: Mammographic screening has improved breast cancer survival in the screened age group. This improved survival has not been seen in older women (>70 years) where screening uptake is low. This study explores the views, knowledge and attitudes of older women towards screening. Methods: Women (>70) were interviewed about breast screening. Interview findings informed the development of a questionnaire which was sent to 1000 women (>70) to quantify their views regarding screening. Results: Twenty-six women were interviewed and a questionnaire designed. The questionnaire response rate was 48.3% (479/992). Over half (52.9%, 241/456) of respondents were unaware they could request mammography by voluntary self-referral and were unaware of how to arrange this. Most (81.5% 383/470) had not attended breast screening since turning 70. Most (75.6%, 343/454) felt screening was beneficial and would attend if invited. Most, (90.1%, 412/457) felt screening should be offered to all women regardless of age or health. Conclusions: There is a lack of knowledge about screening in older women. The majority felt that invitation to screening should be extended to the older age group regardless of age or health. The current under-utilised system of voluntary self referral is not supported by older women

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

Introducing research initiatives into healthcare: What do doctors think?

Background: Current national and international policies emphasize the need to develop research initiatives within our health care system. Institutional biobanking represents a modern, large-scale research initiative that is reliant upon the support of several aspects of the health care organization. This research project aims to explore doctors' views on the concept of institutional biobanking and to gain insight into the factors which impact the development of research initiatives within healthcare systems. Methods: Qualitative research study using semi-structured interviews. The research was conducted across two public teaching hospitals in Sydney, Australia where institutional biobanking was being introduced. Twenty-five participants were interviewed, of whom 21 were medical practitioners at the specialist trainee level or above in a specialty directly related to biobanking; four were key stakeholders responsible for the design and implementation of the biobanking initiative. Results: All participants strongly supported the concept of institutional biobanking. Participants highlighted the discordance between the doctors who work to establish the biobank (the contributors) and the researchers who use it (the consumers). Participants identified several barriers that limit the success of research initiatives in the hospital setting including: the 'resistance to change' culture; the difficulties in engaging health professionals in research initiatives; and the lack of incentives offered to doctors for their contribution. Doctors positively valued the opportunity to advise the implementation team, and felt that the initiative could benefit from their knowledge and expertise. Conclusion: Successful integration of research initiatives into hospitals requires early collaboration between the implementing team and the health care professionals to produce a plan that is sensitive to the needs of the health professionals and tailored to the hospital setting. Research initiatives must consider incentives that encourage doctors to adopt operational responsibility for hospital research initiatives

A Systematic Review of Positive Psychology Interventions (PPIs) to Improve the Health Behaviours, Psychological Wellbeing and/or Physical Health of Police Staff

This review aimed to assess the use of positive psychology interventions (PPIs), such as using positive mantras, expressive writing, or gratitude diaries, to improve the health behaviours, psychological wellbeing and/or physical health of police staff. The review was registered on PROSPERO before 16 electronic databases were searched for published articles between January 1999 and February 2022. Included studies offered PPIs to improve the physical health (body mass index, blood pressure), psychological well-being (stress, anxiety, mood, emotion, depression, self-efficacy), or health behaviours (physical activity, sitting times, dietary habits, alcohol, or tobacco use) of police staff. The mixed methods appraisal tool (MMAT) was used to assess the risk of bias of included papers. The initial search yielded 4560 results; with 3385 papers remaining after duplicates were removed. Of these, 15 studies were included in the final review. Intervention types included mindfulness-based resilience training (n = 11), physical or wellness practice classes (n = 1), role-play and scenario-based interventions (n = 2) and expressive writing (n = 1). Mindfulness-based interventions improved many psychological wellbeing facets such as anxiety, depression, negative affect and quality of life. Limited improvements were observed for some health behaviours such as alcohol consumption and in self-reported general health. Expressive writing and role-play-based interventions were effective in reducing stress and anxiety, however, improvement in depression scores were inconsistent across studies. Positive psychology interventions are promising to support the health and wellbeing of police staff. Future research should investigate their mechanisms of action to support future innovation in support for police wellbeing