Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer

The majority of breast cancers are oestrogen receptor positive (ER+) and are subject to endocrine therapy however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. SLC7A5/SLC3A2 complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Alterations in the expression and function of those amino acid transporters lead to metabolic reprogramming, which contributing to the tumorigenesis and drug resistance. This study aims to assess the effects and roles of SLC7A5/SLC3A2 co-expression in predicting response to endocrine therapy in patients with ER+ breast cancer. The biological and clinical impact of SLC7A5/SLC3A2 co-expression was assessed in large annotated cohorts of ER+/HER2- breast cancer with long-term follow-up at the mRNA and protein levels. In vitro experiments were conducted to investigate the effect of SLC7A5/SLC3A2 knockdown in the proliferation of cancer cells and to the sensitivity to tamoxifen. We found that proliferation-related genes are highly expressed in subgroup of patients with high SLC7A5/SLC3A2, and knockdown of SLC7A5/SLC3A2 decreased proliferation of ER+ breast cancer cells. In patients treated with endocrine therapy, high SLC7A5/SLC3A2 co-expression was associated with poor patient outcome, and depletion of SLC7A5/SLC3A2 using siRNA increased the sensitivity of breast cancer cells to tamoxifen. On the basis of our findings, SLC7A5/SLC3A2 co-expression has the potential of identifying a subgroup of ER+/HER2- breast cancer patients who fail to benefit from endocrine therapy and could guide the choice of other alternative therapy

Data set of smallholder farm households in banana-coffee-based farming systems containing data on farm households, agricultural production and use of organic farm waste

Open Access Journal; Published online: 16 Feb 2021The data was collected in the Karagwe and Kyerwa districts of the Kagera region in north-west Tanzania. It encompasses 150 smallholder farming households, which were interviewed on the composition of their household, agricultural production and use of organic farm waste. The data covers the two previous rainy seasons and the associated vegetation periods between September 2016 and August 2017. The knowledge of experts from the following institutions was included in the discussion on the selection criteria: two local non-profit organisations, i.e., WOMEDA and the MAVUNO Project; the International Institute of Tropical Agriculture (IITA); and the National Land Use Planning Commission (NLUPC). Households were selected for inclusion if all of the following applied to them: 1) less than 10 acres of land (4.7 ha) registered in the village offices, 2) no agricultural training, and 3) decline in the fertility of their land since they started farming (self-reported). We selected 150 smallholder households out of a pool of 5,000 households known to WOMEDA in six divisions of the Kyerwa and Karagwe districts. The questionnaire contained 54 questions. The original language of the survey was Kiswahili. All interviews were audio recorded. The answers were digitalised and translated into English. The data set contains the raw data with 130 quantitative and qualitative variables. For quantitative variables, the only analysis that was made was the conversion of units, e.g., land area was converted from acres to hectares, harvest from buckets to kilograms and then to tons, and heads of livestock to Tropical Livestock Units (TLU). Qualitative variables were summarised into categories. All data has been anonymised. The data set includes geographical variables, household information, agricultural information, gender-specific responsibilities, economic data, farm waste management, and water, energy and food availability (Water-Energy-Food (WEF) Nexus). Variables are written in italics. The following geographical variables are part of the data set: district, division, ward, village, hamlet, longitude, latitude, and altitude. Household information includes start of farming, household size, gender and age of household members. Agricultural information includes land size, size of homegarden, crops, livestock and livestock keeping, trees, and access to forest. Gender-specific responsibilities includes producing and exchanging seeds, weed control, terracing, distributing organic material to the fields, care of annual and perennial crops, harvesting of crops, decisions about the harvest and animal products, selling and buying products, working on their own farm and off-farm, cooking, storing food, collecting and caring for drinking water, washing, and toilet cleaning. Economic data includes distance to the market, journey time to market, transport methods, labourers employed by the household, working off-farm, and assets such as type of house. Variables relevant to the WEF Nexus are drinking water source and treatment, meals per day, months without food, cooking fuel, and type of toilet. Variables on farm waste management are the use of crop residues, food and kitchen waste, livestock manure, cooking ash, animal bones, and human urine and faeces. The data can be potentially reused and further developed for the purpose of agricultural production analysis, socio-economic analysis, comparison to other regions, conceptualisation of waste and nutrient management, establishment of land use concepts, and further analysis on food security and healthy diets

Community views about routine HIV testing and antiretroviral treatment in Botswana: signs of progress from a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The Botswana government began providing free antiretroviral therapy (ART) in 2002 and in 2004 introduced routine HIV testing (RHT) in government health facilities, aiming to increase HIV testing and uptake of ART. There have been concerns that the RHT programme might be coercive, lead to increased partner violence, and drive people away from government health services.</p> <p>Methods</p> <p>We conducted a household survey of 1536 people in a stratified random sample of communities across Botswana, asking about use and experience of government health services, views about RHT, views about ART, and testing for HIV in the last 12 months. Focus groups further discussed issues about ART.</p> <p>Results</p> <p>Some 81% of respondents had visited a government clinic within the last 24 months. Of these 92% were satisfied with the service, 96% felt they were treated with respect and 90% were comfortable about confidentiality. Almost all respondents said they would choose a government clinic for treatment of AIDS.</p> <p>Nearly one half (47%) thought they were at risk of HIV. Those who had experienced partner violence within the last 12 months were more likely to think themselves at risk. One half of those who had visited a government facility in the last 24 months were offered HIV tests, and nearly half were tested. A few (8%) of those who were not asked thought they were tested. Most people (79%) had heard of RHT and 94% were in favour of it. Over one half (55%) of the entire sample had been tested for HIV within the last 12 months, one half of these through RHT. Women were more likely to have been tested.</p> <p>Nearly everyone (94%) had heard of ART and thought it could help AIDS. Focus groups identified problems of access to ART due to distance from treatment centres and long queues in the centres.</p> <p>Conclusion</p> <p>Public awareness and approval of RHT was very high. The high rate of RHT has contributed to the overall high rate of HIV testing. The government's programme to increase HIV testing and uptake of ART is apparently working well. However, turning the tide of the epidemic will also require further concerted efforts to reduce the rate of new HIV infections.</p

SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in oestrogen receptor-positive breast cancer

Purpose: Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The amino acid transporter SLC1A5 has emerging importance as a prognostic marker and potential therapeutic target in various types of cancer. This study aims to investigate its role in luminal breast cancer as a potential predictive marker for endocrine treatment. Methods: SLC1A5 expression was assessed at the transcriptomic and proteomic levels in large, well-characterized cohorts of luminal breast cancer. The sensitivity to endocrine therapy after SLC1A5 knockdown was investigated in vitro, using MCF7 and MDA-MB-175 cell lines. Bioinformatic analyses were performed to study the interacting networks of SLC1A5, and to identify a key co-expressed gene with SLC1A5.Results: here we showed that patients with tumors that highly expressed SLC1A5 associated with a high risk of relapse after endocrine treatment. In vitro, depletion of SLC1A5 increases the sensitivity of luminal breast cancer cells to tamoxifen. TALDO1 was identified as key co-expressed gene with SLC1A5, and in vitro knockdown of SLC1A5 showed reduction in TALDO1 expression. Indeed, TALDO1 was associated with poor clinical outcomes in patients who were subject to endocrine therapy.Conclusion: These findings suggest that metabolic alterations, particularly the interaction between the key amino acid transporter SLC1A5 and metabolic enzyme TALDO1, could affect the sensitivity of endocrine therapy. This study demonstrated the prognostic value of both SLC1A5 and TALDO1 as biomarkers in luminal breast cancer