Transfer functions forQA/QBinternational regulatory limits for the safe transport of radioactive materials.

This paper presents a proposed revision of the International Atomic Energy Agency transport regulations, related to theA1andA2limit values used to determine the radioactive transport classification. Based on the 'Qsystem', a novel methodology was introduced to deriveQAandQBvalues related to scenarios involving external exposure from a distant source. These values are key parameters that respectively represent the total effective dose and total equivalent dose to the skin, from all primary and secondary particles contributing to radiation exposure. The International Working Group (WGA1/A2) is established and associated with the TRANSSC Technical Expert Group on Radiation Protection. A review of theA1andA2values is performed in response to identified limitations within the existingQsystem. The followed approach is based on Monte Carlo simulations that enabled the development of transfer functions aimed at reducing computational time and increasing the flexibility of dose evaluations for any radionuclide with known particle emission spectra. This method allows updating theQAandQBvalues to account for future data evolutions (decay data, fluence-to-dose conversion coefficients) and standardizing the calculation of regulation limits across all referenced radionuclides and scenarios related to external exposure. The transfer functions are established using three Monte Carlo simulation codes-FLUKA, Geant4, and MCNP-and address the previous limitations of the 'Qsystem', reflecting the latest International Commission for Radiation Protection recommendations and improvements in calculation techniques. The results of the WG show consistent agreement across the codes, with minor discrepancies observed at low primary energies due to statistical uncertainties and different handling of stopping power for electrons/positrons in the codes. This revised approach aligns with current standards and recommendations, ensuring that the radiological consequences of transport accidents are acceptable for the newA1andA2limits from a radiological protection perspective.

Proximal humeral fractures with vascular compromise.

Aims: Vascular compromise due to arterial injury is a rare but serious complication of a proximal humeral fracture. The aims of this study were to report its incidence in a large urban population, and to identify clinical and radiological factors which are associated with this complication. We also evaluated the results of the use of our protocol for the management of these injuries. Methods: A total of 3,497 adult patients with a proximal humeral fracture were managed between January 2015 and December 2022 in a single tertiary trauma centre. Their mean age was 66.7 years (18 to 103) and 2,510 (72%) were female. We compared the demographic data, clinical features, and configuration of those whose fracture was complicated by vascular compromise with those of the remaining patients. The incidence of vascular compromise was calculated from national population data, and predictive factors for its occurrence were investigated using univariate analysis. Results: A total of 18 patients (0.5%) had a proximal humeral fracture and clinical evidence of vascular compromise, giving an annual incidence of 0.29 per 100,000 of the population. Their mean age was 68.7 years (45 to 92) and ten (56%) were female. Evidence of a mixed pattern neurological deficit (brachial plexus palsy) (odds ratio (OR) 380.6 (95% CI 85.9 to 1,685.8); p < 0.001), complete separation of the proximal shaft from the humeral head with medial displacement (OR 39.5 (95% CI 14.0 to 111.8); p < 0.001), and a fracture-dislocation (OR 5.0 (95% CI 1.6 to 15.3); p = 0.015) were all associated with an increased risk of associated vascular compromise. A policy of reduction and fixation of the fracture prior to vascular surgical intervention had favourable outcomes without vascular sequelae. Conclusion: The classic signs of distal ischaemia are often absent in patients with proximal injuries to major vessels. We were able to identify specific clinical and radiological 'red flags' which, particularly when present in combination, should increase the suspicion of a fracture with an associated vascular injury, and facilitate early diagnosis and appropriate combined orthopaedic and vascular intervention.

Health risks from radioactive particles on Cumbrian beaches near the Sellafield nuclear site.

A monitoring programme, in place since 2006, continues to recover radioactive particles (<2 mm diameter) and larger objects from the beaches of West Cumbria. The potential risks to members of the public using the beaches are mainly related to prolonged skin contact with or the inadvertent ingestion of small particles. Most particles are classified as either 'beta-rich' or 'alpha-rich' and are detected as a result of their caesium-137 or americium-241 content. Beta-rich particles generally also contain strontium-90, with90Sr:137Cs ratios of up to about 1:1, but typically <0.1:1. Alpha-rich particles contain plutonium isotopes, with Pu:241Amαratios usually around 0.5-0.6:1. 'Beta-rich' particles have the greatest potential to cause localised skin damage if held in stationary contact with the skin for prolonged periods. However, it is concluded that only particles of >106Bq of137Cs, with high90Sr:137Cs ratios, would pose a significant risk of causing acute skin ulceration. No particles of this level of activity have been found. Inadvertent ingestion of a particle will result in the absorption to blood of a small proportion of the radionuclide content of the particle. The subsequent retention of radionuclides in body organs and tissues presents a potential risk of the development of cancer. For 'beta-rich' particles with typical activities (mean 2 × 104Bq137Cs, Sr:Cs ratio of 0.1:1), the estimated committed effective doses are about 30µSv for adults and about 40µSv for 1 year old infants, with lower values for 'alpha-rich' particles of typical activities. The corresponding estimates of lifetime cancer incidence following ingestion for both particle types are of the order of 10-6for adults and up to 10-5for infants. These estimates are subject to substantial uncertainties but provide an indication of the low risks to members of the public.

The Plant Derived 3-3'-Diindolylmethane (DIM) Behaves as CB2 Receptor Agonist in Prostate Cancer Cellular Models.

3-3'-Diindolylmethane (DIM) is a biologically active dimer derived from the endogenous conversion of indole-3-carbinol (I3C), a naturally occurring glucosinolate found in many cruciferous vegetables (i.e., Brassicaceae). DIM was the first pure androgen receptor antagonist isolated from the Brassicaceae family and has been recently investigated for its potential pharmacological use in prostate cancer prevention and treatment. Interestingly, there is evidence that DIM can also interact with cannabinoid receptors. In this context, by considering the well-known involvement of the endocannabinoid system in prostate cancer, we have pharmacologically characterized the properties of DIM on both CB1 and CB2 cannabinoid receptors in two human prostate cancer cell lines: PC3 (androgen-independent/androgen receptor negative) and LNCaP (androgen-dependent). In the PC3 cell line, DIM was able to activate CB2 receptors and potentially associated apoptotic pathways. On the other hand, although DIM was also able to activate CB2 receptors in the LNCaP cell line, no apoptotic effects were observed. Our evidence confirms that DIM is a CB2 receptor ligand and, moreover, it has a potential anti-proliferative effect on androgen-independent/androgen receptor-negative prostate cancer cells.

National Climate Change Risk Assessments to inform adaptation policy priorities and environmental sustainability outcomes: a knowledge systems perspective.

National Climate Change Risk Assessments (CCRAs) have a key role in informing priorities for adaptation policy but face significant challenges due to multiple facets of risk and adaptation. Issues are especially pronounced for meeting goals of environmental sustainability due to the complex dynamics of socio-ecological systems. In practice, a CCRA can therefore differ from its original conceptual blueprint. These challenges are explored from a knowledge systems perspective, focusing on the role of stakeholders/policymakers, risk descriptors, methods, evidence sources, and scientists. A UK case study evaluates recent developments (CCRA3) including identification of policy urgency through adaptation shortfalls and its application to the natural environment. Important science-policy issues are also highlighted regarding inclusion of opportunities, systemic risks, residual risks, and risk tolerance. A general conclusion is that CCRAs inevitably leave open questions which lead back to their evolving role in the science-policy interface. A knowledge systems perspective identifies CCRAs as open, adaptive, reflexive processes that help redefine interpretations of risk and adaptation, rather than just providing a specific policy-relevant product. This perspective identifies scope for progressive refinement of CCRAs to enhance collective science-policy adaptive capacity whilst also engaging wider society. For environmental sustainability, this open process can be used to iteratively redefine robust future pathways and system reference conditions that also better reflect evolving societal perceptions and tolerance on sustainability risk in the face of climate change.

Compartment syndrome of the hand following iatrogenic intra-arterial administration of epinephrine during cardiopulmonary resuscitation.

A 26-year-old woman developed acute compartment syndrome (ACS) of her right hand secondary to reperfusion syndrome. She suffered an out-of-hospital cardiac arrest following a pregabalin overdose. Attending paramedics mistakenly gave intra-arterial epinephrine into her right brachial artery. On resolution of her brachial artery spasm, she developed a reperfusion injury to her right hand and subsequently ACS. A four-incision fasciotomy with carpal tunnel decompression was performed and was successful in reversing focal ischaemia and an irreversible functional deficit. This case demonstrates an unusual case of hand ACS secondary to temporary limb ischaemia and reperfusion syndrome following iatrogenic intra-arterial epinephrine administration. We also summarise the current available literature on ACS of the hand including the aetiology, treatment and use of an intracompartmental monitor.

Cost-effectiveness of the reverse total shoulder arthroplasty. Does indication affect outcome?

BACKGROUND: The primary aim of this study was to determine the cost-effectiveness of the reverse total shoulder arthroplasty in a prospective cohort of patients over a two-year post-operative period. METHODS: Patients who underwent reverse total shoulder arthroplasty were prospectively monitored for 24 months post-operatively using the Oxford Shoulder Score, Disabilities of the Arm, Shoulder and Hand questionnaire and EuroQol 5-dimensional questionnaire. Any complications or use of health care resources were recorded. The incremental cost-effectiveness ratio was used to express the cost per quality-adjusted life year gained. RESULTS: Sixty-seven patients were analysed, 46 primary reverse total shoulder arthroplasty for cuff arthropathy and 21 revisions from previous arthroplasty. Both indications had comparable peri-operative shoulder scores without significant difference. Using the mean change of EuroQol 5-dimensional questionnaire at one year, the incremental cost-effectiveness ratio was calculated at £16,827.43 per quality-adjusted life year, decreasing to £8313.48 per quality-adjusted life year at two years. Primary was associated with a lower incremental cost-effectiveness ratio at two years (primary £7596.76 vs. revision £11,748.51). The estimated post-operative life expectancy of the cohort was 6.9 years with a projected cost per quality-adjusted life year of £2438.78. CONCLUSIONS: Reverse total shoulder arthroplasty provides a cost-effective intervention with excellent patient outcomes at two years post-operatively.

Patient-reported outcomes after corrective osteotomy for a symptomatic malunion of the distal radius.

AIMS: The primary aim of this study was to describe patient satisfaction and health-related quality of life (HRQoL) following corrective osteotomy for a symptomatic malunion of the distal radius. METHODS: We retrospectively identified 122 adult patients from a single centre over an eight-year period who had undergone corrective osteotomy for a symptomatic malunion of the distal radius. The primary long-term outcome was the Patient-Rated Wrist Evaluation (PRWE) score. Secondary outcomes included the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, the EQ-5D-5L score, complications, and the Net Promoter Score (NPS). Multivariate regression analysis was used to determine factors associated with the PRWE score. RESULTS: Long-term outcomes were available for 89 patients (72%). The mean age was 57 years (SD 15) and 68 were female (76%). The median time from injury to corrective osteotomy was nine months (interquartile range (IQR) 6 to 13). At a mean follow-up of six years (1 to 11) the median PRWE score was 22 (IQR 7 to 40), the median QuickDASH score was 11.4 (IQR 2.3 to 31.8), and the median EQ-5D-5L score was 0.84 (IQR 0.69 to 1). The NPS was 69. Multivariate regression analysis showed that the presence of an associated ulnar styloid fracture was the only significant independent factor associated with a worse PRWE score when adjusting for confounding variables (p = 0.004). CONCLUSION: We found that corrective osteotomy for malunion of the distal radius can result in good functional outcomes and high levels of patient satisfaction. However, the presence of an ulnar styloid fracture may adversely affect function. Level of Evidence: III (cohort study). Cite this article: Bone Joint J 2020;102-B(11):1542-1548.

Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion.

The anticancer effects of the omega-3 long chain polyunsaturated fatty acids (LCPUFA), EPA and DHA may be due, at least in part, to conversion to their respective endocannabinoid derivatives, eicosapentaenoyl-ethanolamine (EPEA) and docosahexaenoyl-ethanolamine (DHEA). Here, the effects of EPEA and DHEA and their parent compounds, EPA and DHA, on breast cancer (BC) cell function was examined. EPEA and DHEA exhibited greater anti-cancer effects than EPA and DHA in two BC cells (MCF-7 and MDA-MB-231) whilst displaying no effect in non-malignant breast cells (MCF-10a). Both BC lines expressed CB1/2 receptors that were responsible, at least partly, for the observed anti-proliferative effects of the omega-3 endocannabinoids as determined by receptor antagonism studies. Additionally, major signalling mechanisms elicited by these CB ligands included altered phosphorylation of p38-MAPK, JNK, and ERK proteins. Both LCPUFAs and their endocannabinoids attenuated the expression of signal proteins in BC cells, albeit to different extents depending on cell type and lipid effectors. These signal proteins are implicated in apoptosis and attenuation of BC cell migration and invasiveness. Furthermore, only DHA reduced in vitro MDA-MB-231 migration whereas both LCPUFAs and their endocannabinoids significantly inhibited invasiveness. This finding was consistent with reduced integrin ß3 expression observed with all treatments and reduced MMP-1 and VEGF with DHA treatment. Attenuation of cell viability, migration and invasion of malignant cells indicates a potential adjunct nutritional therapeutic use of these LCPUFAs and/or their endocannabinoids in treatment of breast cancer.

Assessing climate change risks to the natural environment to facilitate cross-sectoral adaptation policy.

Climate change policy requires prioritization of adaptation actions across many diverse issues. The policy agenda for the natural environment includes not only biodiversity, soils and water, but also associated human benefits through agriculture, forestry, water resources, hazard alleviation, climate regulation and amenity value. To address this broad agenda, the use of comparative risk assessment is investigated with reference to statutory requirements of the UK Climate Change Risk Assessment. Risk prioritization was defined by current adaptation progress relative to risk magnitude and implementation lead times. Use of an ecosystem approach provided insights into risk interactions, but challenges remain in quantifying ecosystem services. For all risks, indirect effects and potential systemic risks were identified from land-use change, responding to both climate and socio-economic drivers, and causing increased competition for land and water resources. Adaptation strategies enhancing natural ecosystem resilience can buffer risks and sustain ecosystem services but require improved cross-sectoral coordination and recognition of dynamic change. To facilitate this, risk assessments need to be reflexive and explicitly assess decision outcomes contingent on their riskiness and adaptability, including required levels of human intervention, influence of uncertainty and ethical dimensions. More national-scale information is also required on adaptation occurring in practice and its efficacy in moderating risks.This article is part of the theme issue 'Advances in risk assessment for climate change adaptation policy'.

Advances in risk assessment for climate change adaptation policy.

Climate change risk assessment involves formal analysis of the consequences, likelihoods and responses to the impacts of climate change and the options for addressing these under societal constraints. Conventional approaches to risk assessment are challenged by the significant temporal and spatial dynamics of climate change; by the amplification of risks through societal preferences and values; and through the interaction of multiple risk factors. This paper introduces the theme issue by reviewing the current practice and frontiers of climate change risk assessment, with specific emphasis on the development of adaptation policy that aims to manage those risks. These frontiers include integrated assessments, dealing with climate risks across borders and scales, addressing systemic risks, and innovative co-production methods to prioritize solutions to climate challenges with decision-makers. By reviewing recent developments in the use of large-scale risk assessment for adaptation policy-making, we suggest a forward-looking research agenda to meet ongoing strategic policy requirements in local, national and international contexts.This article is part of the theme issue 'Advances in risk assessment for climate change adaptation policy'.

Changes in climate variability with reference to land quality and agriculture in Scotland.

Classification and mapping of land capability represents an established format for summarising spatial information on land quality and land-use potential. By convention, this information incorporates bioclimatic constraints through the use of a long-term average. However, climate change means that land capability classification should also have a dynamic temporal component. Using an analysis based upon Land Capability for Agriculture in Scotland, it is shown that this dynamism not only involves the long-term average but also shorter term spatiotemporal patterns, particularly through changes in interannual variability. Interannual and interdecadal variations occur both in the likelihood of land being in prime condition (top three capability class divisions) and in class volatility from year to year. These changing patterns are most apparent in relation to the west-east climatic gradient which is mainly a function of precipitation regime and soil moisture. Analysis is also extended into the future using climate results for the 2050s from a weather generator which show a complex interaction between climate interannual variability and different soil types for land quality. In some locations, variability of land capability is more likely to decrease because the variable climatic constraints are relaxed and the dominant constraint becomes intrinsic soil properties. Elsewhere, climatic constraints will continue to be influential. Changing climate variability has important implications for land-use planning and agricultural management because it modifies local risk profiles in combination with the current trend towards agricultural intensification and specialisation.

In search of serenity: religious struggle among patients hospitalized for suspected acute coronary syndrome.

Hospitalization for a sudden cardiac event is a frightening experience, one that is often marked by uncertainty about health status, fear of recurrent cardiac problems, and related existential, religious, and spiritual concerns. Religious struggle, reflecting tension and strain regarding religious and spiritual issues, may arise in response to symptoms of acute coronary syndrome (ACS). The present study examined the prevalence and types of religious struggle using the Brief RCOPE, as well as associations between religious struggle, psychological distress, and self-reported sleep habits among 62 patients hospitalized with suspected ACS. Fifty-eight percent of the sample reported some degree of religious struggle. Questioning the power of God was the most frequently endorsed struggle. Those struggling religiously reported significantly more symptoms of anxiety, depression, and sleep disturbance. Non-White participants endorsed greater use of positive religious coping strategies and religious struggle. Results suggest that patients hospitalized for suspected ACS experiencing even low levels of religious struggle might benefit from referral to a hospital chaplain or appropriately trained mental health professional for more detailed religious and spiritual assessment. Practical means of efficiently screening for religious struggle during the often brief hospitalization period for suspected ACS are discussed.

Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators.

Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB(½), TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating non-CBR signaling pathways. Cannabinoids-endocannabinoids are anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals. They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, PPARs, VEGF, NF-κB, p8, CHOP, TRB3 and pro-apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle arrest, autophagy, apoptosis and tumour inhibition. Paradoxically they are pro-proliferative and anti-apoptotic in some cancers. Differences in receptor expression and concentrations of cannabinoids in cancer and immune cells can elicit anti- or pro-cancer effects through different signal cascades (p38MAPK or PI3/AKT). Similarities between effects of cannabinoids-endocannabinoids, omega-3 LCPUFA and CLAs/CLnAs as anti-inflammatory, antiangiogenic, anti-invasive anti-cancer agents indicate common signaling pathways. Evidence in vivo and in vitro shows EPA and DHA can form endocannabinoids that: (i) are ligands for CB(½) receptors and possibly TRPV-1, (ii) have non-receptor mediated bioactivity, (iii) induce cell cycle arrest, (iii) increase autophagy and apoptosis, and (iv) augment chemotherapeutic actions in vitro. They can also form bioactive, eicosanoid-like products that appear to be non-CBR ligands but have effects on PPARs and NF-kB transcription factors. The use of cannabinoids in cancer treatment is currently limited to chemo- and radio-therapy-associated nausea and cancer-associated pain apart from one trial on brain tumours in patients. Further clinical studies are urgently required to determine the true potential of these intriguing, low toxicity compounds in cancer therapy. Particularly in view of their synergistic effects with chemotherapeutic agents similar to that observed for n-3 LCPUFA.

Influence of seasonal weather and climate variability on crop yields in Scotland.

The climatic sensitivity of four important agriculture crops (wheat, barley, oats, potatoes) in a northern temperate bioclimatic region is investigated using national-level yield data for 1963-2005. The climate variables include monthly and annual meteorological data, derived bioclimatic metrics, and the North Atlantic Oscillation index. Statistical analysis shows that significant relationships between yield and climate vary depending on the crop type and month but highlight the influence of precipitation (negative correlation) and sunshine duration (positive correlation) rather than temperature. Soil moisture deficit is shown to be a particular useful indicator of yield with drier summers providing the best yields for Scotland as a whole. It is also tentatively inferred that the sensitivity of these crops, particularly wheat and barley, to soil moisture deficits has increased in recent years. This suggests that improved crop yields are optimised for dry sunny years despite the continued prevalence of considerable inter-annual variability in seasonal weather.

Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines.

The omega-3 fatty acid ethanolamides, docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), displayed greater anti-proliferative potency than their parent omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in LNCaP and PC3 prostate cancer cells. DHEA and EPEA activated cannabinoid CB(1) and CB(2) receptors in vitro with significant potency, suggesting that they are endocannabinoids. Both LNCaP and PC3 cells expressed CB(1) and CB(2) receptors, and the CB(1)- and CB(2)-selective antagonists, AM281 and AM630, administered separately or together, reduced the anti-proliferative potencies of EPEA and EPA but not of DHEA or DHA in PC3 cells and of EPA but not of EPEA, DHEA or DHA in LNCaP cells. Even so, EPEA and EPA may not have inhibited PC3 or LNCaP cell proliferation via cannabinoid receptors since the anti-proliferative potency of EPEA was well below the potency it displayed as a CB(1) or CB(2) receptor agonist. Indeed, these receptors may mediate a protective effect because the anti-proliferative potency of DHEA in LNCaP and PC3 cells was increased by separate or combined administration of AM281 and AM630. The anandamide-metabolizing enzyme, fatty acid amide hydrolase (FAAH), was highly expressed in LNCaP but not PC3 cells. Evidence was obtained that FAAH metabolizes EPEA and DHEA and that the anti-proliferative potencies of these ethanolamides in LNCaP cells can be enhanced by inhibiting this enzyme. Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents.

Altered DNA methylation is associated with docetaxel resistance in human breast cancer cells.

Docetaxel is an effective chemotherapy drug to treat breast cancer but the underlying molecular mechanisms of drug resistance are not fully understood. DNA methylation is an epigenetic event, involved in the control of gene expression, which is known to play an important role in cancer and chemotherapy drug resistance. To investigate the role of DNA methylation in docetaxel resistance in breast cancer we used two human breast cancer cell lines (MCF-7 and MDA-MB-231) that were made resistant to docetaxel. Docetaxel-resistant sub-lines were treated with different concentrations of decitabine. Global methylation and DNA methyltransferase (DNMT) activity was measured using an ELISA-based assay. Quantitative real-time PCR was used to study DNMT gene expression. Cell viability was studied by MTT assay. Global methylation was increased in MCF-7 but not significantly changed in MDA-MB-231 docetaxel-resistant cells. Decreased DNMT activity and decreased DNMT1 and DNMT3b mRNA expression was associated with docetaxel resistance in both cell lines. To investigate how the components of the DNA methylation machinery may contribute towards docetaxel resistance, decitabine (5-aza-2'-deoxycytidine), an inhibitor of DNA methylation, was used. Decitabine treatment decreased global methylation, DNMT activity and DNMT1, DNMT3a and DNMT3b mRNA expression in MDA-MB-231 docetaxel-resistant cells. In contrast, decitabine-treated MCF-7 docetaxel-resistant cells showed increased DNMT1, DNMT3a and DNMT3b mRNA expression indicating a cell line specific effect of decitabine. Decitabine treatment increased resistance in MCF-7 docetaxel-resistant cells and in the parental MCF-7 and MDA-MB231 docetaxel-sensitive cell lines, however, it did not alter response to docetaxel in MDA-MB-231 docetaxel-resistant cells. This study demonstrates that changes in the DNA methylation machinery are associated with resistance to docetaxel in breast cancer cells. The use of epigenetic therapies, as a strategy to overcome drug resistance, needs to be investigated more fully to determine their effectiveness in different cancers and for different chemotherapy drugs.

Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids.

The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs. Although experimental evidence for the potential beneficial role of polyunsaturated fatty acids (PUFAs) in enhancing the effectiveness of various chemotherapeutic agents in animal models and in cell culture studies is increasing, there are only a few reports that have shown supportive evidence for linking these natural compounds with augmentation of anticancer chemotherapeutics in human trials. This review presents evidence for a commonality in the proposed molecular mechanisms of action elicited by various PUFAs believed to be responsible for their enhancement of the effectiveness of anticancer chemotherapy, specifically in breast and prostate cancers, and reviews laboratory and animal studies and few reported human clinical trials. It concludes that sufficient evidence is available to suggest that major clinical trials with these natural compounds as adjuncts to standard therapies should be undertaken as a priority.

Effects of decitabine on the expression of selected endogenous control genes in human breast cancer cells.

To quantify gene expression levels, appropriate controls have to be used to adjust for experimental variation. Endogenous control genes are widely used as they are stably expressed independent of cell cycle and experimental conditions, however, they can be altered upon drug treatment. DNA methylation is widely studied in chemotherapy drug resistance and the DNA methylation inhibitor decitabine showed promising results reversing drug resistance in cancer. We aimed to investigate the effect of different decitabine concentrations on the expression of selected endogenous control genes (GAPDH, 18S rRNA, PPIA, RPL13A, OAZ1) in two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) compared to untreated cells. In MCF-7 cells, 18S rRNA remained stable, however, GAPDH, PPIA and OAZ1 gene expression was increased after treatment. RPL13A was stably expressed at 8 muM decitabine but was increased at lower drug concentrations. In MDA-MB-231 cells, GAPDH levels remained relatively stable following decitabine treatment and so was PPIA expression at low decitabine concentrations. Decitabine increased 18S rRNA, RPL13A and OAZ1 gene expression. In this study, we observed cell line specific effects of decitabine and suggest that 18S rRNA is most suitable to use in MCF-7 cells, while GAPDH is recommended to use in MDA-MB-231 cells during decitabine treatment.