The tumour-derived extracellular vesicle proteome varies by endometrial cancer histology and is confounded by an obesogenic environment.

Endometrial cancer, the most common gynaecological cancer worldwide, is closely linked to obesity and metabolic diseases, particularly in younger women. New circulating biomarkers have the potential to improve diagnosis and treatment selections, which could significantly improve outcomes. Our approach focuses on extracellular vesicle (EV) biomarker discovery by directly profiling the proteome of EVs enriched from frozen biobanked endometrial tumours.

Liposome-enabled bufalin and doxorubicin combination therapy for trastuzumab-resistant breast cancer with a focus on cancer stem cells.

Breast cancer stem cells (BCSCs) play a key role in therapeutic resistance in breast cancer treatments and disease recurrence. This study aimed to develop a combination therapy loaded with pH-sensitive liposomes to kill both BCSCs and the okbulk cancer cells using trastuzumab-sensitive and resistant human epidermal growth factor receptor 2 positive (HER2) breast cancer cell models. The anti-BCSCs effect and cytotoxicity of all-trans retinoic acid, salinomycin, and bufalin alone or in combination with doxorubicin were compared in HER2 cell line BT-474 and a validated trastuzumab-resistant cell line, BT-474R.

The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is a condition that arises from dysfunction or early depletion of the ovarian follicle pool accompanied by an earlier-than-normal loss of fertility in young women. Oxidative stress has been suggested as an important factor in the decline of fertility in women and POI. In this review, we discuss the mechanisms of oxidative stress implicated in ovarian ageing and dysfunction in relation to POI, in particular mitochondrial dysfunction, apoptosis and inflammation.

Genetic discrimination by insurance companies in Aotearoa New Zealand: experiences and views of health professionals.

Aims: Genetic discrimination in insurance is a significant clinical, research and consumer issue. Recently, the Australian life insurance industry introduced a partial moratorium on the use of genetic test results. However, in Aotearoa New Zealand, both life and health insurers can still use genetic results legally to discriminate against applicants.

Stability of trastuzumab during nanomedicine formulation using SEC-HPLC coupled with polyacrylamide gel electrophoresis.

The anti-HER2 antibody trastuzumab has been proven to be an effective targeting ligand for drug delivery. This study investigates the structural integrity of trastuzumab under different stress factors in formulation development and its long-term stability. A validated size exclusion high performance liquid chromatographic (SEC-HPLC) method was first developed.

Genomic discrimination in New Zealand health and life insurance. AGenDA: Against Genomic Discrimination in Aotearoa.

Nil.

A Predictor of Early Disease Recurrence in Patients With Breast Cancer Using a Cell-free RNA and Protein Liquid Biopsy.

Introduction: Circulating biomarkers have been increasingly used in the clinical management of breast cancer. The present study evaluated whether RNAs and a protein present in the plasma of patients with breast cancer might have utility as prognostic biomarkers complementary to existing clinical tests.

Patients And Methods: We performed microarray profiling of small noncoding RNAs in plasma samples from 30 patients with breast cancer and 10 control individuals.

Human Sensory LTP Predicts Memory Performance and Is Modulated by the ValMet Polymorphism.

: Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance.

Genomic medicine must reduce, not compound, health inequities: the case for hauora-enhancing genomic resources for New Zealand.

Precision medicine seeks to draw on data from both individuals and populations across disparate domains to influence and support diagnosis, management and prevention in healthcare at the level of the individual patient and their family/whānau. Central to this initiative is incorporating the effects of the inherent variation that lies within genomes and can influence health outcomes. Identifying and interpreting such variation requires an accurate, valid and representative dataset to firstly define what variants are present and then assess the potential relevance for the health of a person, their family/whānau and the wider community to which they belong.

Discordant association of the CREBRF rs373863828 A allele with increased BMI and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand.

Aims/hypothesis: The A (minor) allele of CREBRF rs373863828 has been associated with increased BMI and reduced risk of type 2 diabetes in the Samoan populations of Samoa and American Samoa. Our aim was to test rs373863828 for associations with BMI and the odds of type 2 diabetes, gout and chronic kidney disease (CKD) in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand.

Methods: Linear and logistic regression models were used to analyse the association of the A allele of CREBRF rs373863828 with BMI, log-transformed BMI, waist circumference, type 2 diabetes, gout and CKD in 2286 adults.

Gene expression profiling of breast tumours from New Zealand patients.

Aims: New Zealand has one of the highest rates of breast cancer incidence in the world. We investigated the gene expression profiles of breast tumours from New Zealand patients, compared them to gene expression profiles of international breast cancer cohorts and identified any associations between altered gene expression and the clinicopathological features of the tumours.

Methods: Affymetrix microarrays were used to measure the gene expression profiles of 106 breast tumours from New Zealand patients.

Gene-by-environment interactions of the CLOCK, PEMT, and GHRELIN loci with average sleep duration in relation to obesity traits using a cohort of 643 New Zealand European children.

Objectives: Modern technology may have desensitised the 'biological clock' to environmental cues, disrupting the appropriate co-ordination of metabolic processes. Susceptibility to misalignment of circadian rhythms may be partly genetically influenced and effects on sleep quality and duration could predispose to poorer health outcomes. Shorter sleep duration is associated with obesity traits, which are brought on by an increased opportunity to eat and/or a shift of hormonal profile promoting hunger.

MicroRNA profiling of ovarian granulosa cell tumours reveals novel diagnostic and prognostic markers.

Background: The aim of this study was to explore the clinical utility of microRNAs (miRNAs) as improved markers of ovarian granulosa cell tumours (GCTs) for cancer diagnosis and prognosis prediction. Current histopathological and genetic markers, such as the presence of a gene mutation to distinguish between the two major subtypes are not wholly accurate and as such novel biomarkers are warranted.

Methods: The miRNA expression profiles of five formalin-fixed, paraffin-embedded (FFPE) adult-GCTs and five juvenile-GCTs were assessed using Affymetrix miRNA 3.

Gene-by-Activity Interactions on Obesity Traits of 6-Year-Old New Zealand European Children: A Children of SCOPE Study.

Purpose: The decline of physical activity in children is considered an important determinant to explain the rising rates of obesity. However, this risk may be augmented in children who are genetically susceptible to increased weight gain. We hypothesized that a sedentary lifestyle and moderate activity will interact with genetic loci, resulting in differential effects in relation to obesity risk.

Analysis of association of gene variants with obesity traits in New Zealand European children at 6 years of age.

Childhood obesity is a public health problem, which is associated with a long-term increased risk of cardiovascular disease and premature mortality. Several gene variants have previously been identified that have provided novel insights into biological factors that contribute to the development of obesity. As obesity tracks through childhood into adulthood, identification of the genetic factors for obesity in early life is important.

Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells.

This study aimed at development of poly (lactic-co-glycolic acid) (PLGA) nanoparticles embedded with paclitaxel and coated with hyaluronic acid (HA-PTX-PLGA) to actively target the drug to a triple negative breast cancer cells. Nanoparticles were successfully fabricated using a modified oil-in-water emulsion method. The effect of various formulations parameters on the physicochemical properties of the nanoparticles was investigated.

Characterizing nuclear and mitochondrial DNA in spent embryo culture media: genetic contamination identified.

Objective: To characterize nuclear and mitochondrial DNA (mtDNA) in spent culture media from normally developing blastocysts to determine whether it could be used for noninvasive genetic assessment.

Design: Prospective embryo cohort study.

Setting: Academic center and private in vitro fertilization (IVF) clinic.

Multimodal Assessment of Estrogen Receptor mRNA Profiles to Quantify Estrogen Pathway Activity in Breast Tumors.

Background: Molecular markers have transformed our understanding of the heterogeneity of breast cancer and have allowed the identification of genomic profiles of estrogen receptor (ER)-α signaling. However, our understanding of the transcriptional profiles of ER signaling remains inadequate. Therefore, we sought to identify the genomic indicators of ER pathway activity that could supplement traditional immunohistochemical (IHC) assessments of ER status to better understand ER signaling in the breast tumors of individual patients.

Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: evidence and potential clinical use.

The ability to screen embryos for aneuploidy or inherited disorders in a minimally invasive manner may represent a major advancement for the future of embryo viability assessment. Recent studies have demonstrated that both blastocoele fluid and embryo culture medium contain genetic material, which can be isolated and subjected to downstream genetic analysis. The blastocoele fluid may represent an alternative source of nuclear DNA for aneuploidy testing, although the degree to which the isolated genetic material is solely representative of the developing embryo is currently unclear.

A novel EGR-1 dependent mechanism for YB-1 modulation of paclitaxel response in a triple negative breast cancer cell line.

Chemotherapy with taxanes such as paclitaxel (PTX) is a key component of triple negative breast cancer (TNBC) treatment. PTX is used in combination with other drugs in both the adjuvant setting and in advanced breast cancer. Because a proportion of patients respond poorly to PTX or relapse after its use, a greater understanding of the mechanisms conferring resistance to PTX is required.

Oocyte mitochondrial deletions and heteroplasmy in a bovine model of ageing and ovarian stimulation.

Study Hypothesis: Maternal ageing and ovarian stimulation result in the accumulation of mitochondrial DNA (mtDNA) deletions and heteroplasmy in individual oocytes from a novel bovine model for human assisted reproductive technology (ART).

Study Finding: The levels of mtDNA deletions detected in oocytes increased with ovarian ageing. Low levels of mtDNA heteroplasmy were apparent across oocytes and no relationship was identified with respect to ovarian ageing or ovarian stimulation.

Nanoparticle therapeutics: Technologies and methods for overcoming cancer.

It is anticipated that by 2030 approximately 13 million people will die of cancer. Common cancer therapy often fails due to the development of multidrug resistance (MDR), resulting in high morbidity and poor patient prognosis. Nanotechnology seeks to use drug delivery vehicles of 1-100 nm in diameter, made up of several different materials to deliver anti-cancer drugs selectively to cancer cells and potentially overcome MDR.