Spatial intra-tumour heterogeneity and treatment-induced genomic evolution in oesophageal adenocarcinoma: implications for prognosis and therapy.

Background: Oesophageal adenocarcinoma (OAC) is a highly heterogeneous cancer with poor survival. Standard curative treatment is chemotherapy with or without radiotherapy followed by oesophagectomy. Genomic heterogeneity is a feature of OAC and has been linked to treatment resistance.

Endometrial cancer PDX-derived organoids (PDXOs) and PDXs with FGFR2c isoform expression are sensitive to FGFR inhibition.

Endometrial cancer (EC) patients with metastatic/recurrent disease have limited treatment options and poor survival outcomes. Recently, we discovered the FGFR2c splice isoform is associated with poor prognosis in EC patients. Here we report the establishment of 16 EC patient-derived xenografts (PDX)-derived organoids (PDXOs) with or without FGFR2c expression.

The oesophageal adenocarcinoma tumour immune microenvironment dictates outcomes with different modalities of neoadjuvant therapy - results from the AGITG DOCTOR trial and the cancer evolution biobank.

A plateau in treatment effect can be seen for the current 'one-size-fits-all' approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, the tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed to understand the overall immune-based mechanisms underlying treatment responses and patient outcomes in OAC, and in relation to neoadjuvant therapy modality.

Circulating Tumor DNA: A Promising Biomarker for Predicting Recurrence in Patients with BRAF-Negative Melanoma.

For patients with BRAF wild-type stage III and IV melanoma, there is an urgent clinical need to identify prognostic biomarkers and biomarkers predictive of treatment response. Circulating tumor DNA (ctDNA) is emerging as a blood-based biomarker and has shown promising results for many cancers, including melanoma. The purpose of this study was to identify targetable, tumor-derived mutations in patient blood that may lead to treatment alternatives and improved outcomes for patients with BRAF-negative melanoma.

C-reactive protein is a prognostic biomarker in pancreatic ductal adenocarcinoma patients.

Aim: The 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is approximately 11% and has only improved marginally over the last three decades. For operable PDAC, resection and adjuvant FOLFIRINOX chemotherapy is standard of care. There is growing interest in perioperative regimens to improve outcomes.

Accelerating genomic workflows using NVIDIA Parabricks.

Background: As genome sequencing becomes better integrated into scientific research, government policy, and personalized medicine, the primary challenge for researchers is shifting from generating raw data to analyzing these vast datasets. Although much work has been done to reduce compute times using various configurations of traditional CPU computing infrastructures, Graphics Processing Units (GPUs) offer opportunities to accelerate genomic workflows by orders of magnitude. Here we benchmark one GPU-accelerated software suite called NVIDIA Parabricks on Amazon Web Services (AWS), Google Cloud Platform (GCP), and an NVIDIA DGX cluster.

Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures.

From biomedical cloud platforms to microservices: next steps in FAIR data and analysis.

The biomedical research community is investing heavily in biomedical cloud platforms. Cloud computing holds great promise for addressing challenges with big data and ensuring reproducibility in biology. However, despite their advantages, cloud platforms in and of themselves do not automatically support FAIRness.

Playing catch-up in building an open research commons.

As efforts advance around the globe, the US falls behind.

Comparison of actionable events detected in cancer genomes by whole-genome sequencing, in silico whole-exome and mutation panels.

Background: Next-generation sequencing is used in cancer research to identify somatic and germline mutations, which can predict sensitivity or resistance to therapies, and may be a useful tool to reveal drug repurposing opportunities between tumour types. Multigene panels are used in clinical practice for detecting targetable mutations. However, the value of clinical whole-exome sequencing (WES) and whole-genome sequencing (WGS) for cancer care is less defined, specifically as the majority of variants found using these technologies are of uncertain significance.

ctDNA as a biomarker of progression in oesophageal adenocarcinoma.

Background: The incidence of oesophageal adenocarcinoma (OAC) is rapidly increasing and despite improvements in treatment, the 5-year survival rate remains poor. Prognostic biomarkers that address the genomic heterogeneity in this highly complex disease will aid the development of precision therapeutics and improve patient survival. The aim of this study was to determine whether circulating tumour DNA (ctDNA) has prognostic significance as a biomarker in OAC patients.

Breastfeeding booklet in prison institutions: initiative for promotion, protection and support.

Objectives: to understand the use of the booklet on breastfeeding in prison in times of COVID 19 by managers and health professionals who work with pregnant and breastfeeding women deprived of their liberty.

Methods: this is a descriptive, exploratory research with a qualitative approach, carried out from March to December 2020. Thirteen professionals who work in Brazilian prison institutions participated in the study and answered a semi-structured interview.

Patient-derived xenograft models capture genomic heterogeneity in endometrial cancer.

Background: Endometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprises four molecular subtypes with differing etiology, prognoses, and responses to chemotherapy. In the future, clinical trials testing new single agents or combination therapies will be targeted to the molecular subtype most likely to respond.

Characterizing the Heterogeneity of Small Extracellular Vesicle Populations in Multiple Cancer Types an Ultrasensitive Chip.

Identifying small extracellular vesicle (sEV) subpopulations based on their different molecular signatures could potentially reveal the functional roles in physiology and pathology. However, it is a challenge to achieve this aim due to the nano-sized dimensions of sEVs, low quantities of biological cargo each sEV carries, and our incomplete knowledge of identifying features capable of separating heterogeneous sEV subpopulations. Here, a sensitive, multiplexed, and nano-mixing-enhanced sEV subpopulation characterization platform (ESCP) is proposed to precisely determine the sEV phenotypic heterogeneity and understand the role of sEV heterogeneity in cancer progression and metastasis.

Radiomics Biomarkers Correlate with CD8 Expression and Predict Immune Signatures in Melanoma Patients.

Treatment for metastatic melanoma includes targeted and/or immunotherapy. Although many patients respond, only a subset has complete response. As late-stage patients often have multiple tumors in difficult access sites, non-invasive techniques are necessary for the development of predictive/prognostic biomarkers.

Pathogenic germline variants are associated with poor survival in stage III/IV melanoma patients.

Patients with late stage resected cutaneous melanoma have poor overall survival (OS) and experience irreversible adverse events from systemic therapy. There is a clinical need to identify biomarkers to predict outcome. Performing germline/tumour whole-exome sequencing of 44 stage III/IV melanoma patients we identified pathogenic germline mutations in CDKN2A, CDK4, ATM, POLH, MRE11A, RECQL4 and XPC, affecting 7/44 patients.

FAIRshake: Toolkit to Evaluate the FAIRness of Research Digital Resources.

As more digital resources are produced by the research community, it is becoming increasingly important to harmonize and organize them for synergistic utilization. The findable, accessible, interoperable, and reusable (FAIR) guiding principles have prompted many stakeholders to consider strategies for tackling this challenge. The FAIRshake toolkit was developed to enable the establishment of community-driven FAIR metrics and rubrics paired with manual and automated FAIR assessments.

Combined use of subclinical hydroxyurea and CHK1 inhibitor effectively controls melanoma and lung cancer progression, with reduced normal tissue toxicity compared to gemcitabine.

Drugs such as gemcitabine that increase replication stress are effective chemotherapeutics in a range of cancer settings. These drugs effectively block replication and promote DNA damage, triggering a cell cycle checkpoint response through the ATR-CHK1 pathway. Inhibiting this signalling pathway sensitises cells to killing by replication stress-inducing drugs.

Complex structural rearrangements are present in high-grade dysplastic Barrett's oesophagus samples.

Background: Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett's oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals.

Bcl-2 inhibitors enhance FGFR inhibitor-induced mitochondrial-dependent cell death in FGFR2-mutant endometrial cancer.

Endometrial cancer is the most commonly diagnosed gynaecological malignancy. Unfortunately, 15-20% of women demonstrate persistent or recurrent tumours that are refractory to current chemotherapies. We previously identified activating mutations in fibroblast growth factor receptor 2 (FGFR2) in 12% (stage I/II) to 17% (stage III/IV) endometrioid ECs and found that these mutations are associated with shorter progression-free and cancer-specific survival.

Gene Expression Array Analysis to Identify Candidate Tumor Suppressor Genes in Melanoma.

Melanoma is a complex multifactorial disease; therefore, a combination of various approaches is necessary to girt all aspects of its biology and identify the many different genes and factors involved in its etiology.Epigenetic regulation of tumor suppressor genes (TSGs) has been shown to play a central role in melanomagenesis. Here, we describe a new pipeline based on an integrative and comparative analysis of several array platform, post-demethylation treatment expression data, methylation array, and constitutive mRNA expression analysis to identify novel TSGs frequently methylated in melanoma.

Should biomedical research be like Airbnb?

The thesis presented here is that biomedical research is based on the trusted exchange of services. That exchange would be conducted more efficiently if the trusted software platforms to exchange those services, if they exist, were more integrated. While simpler and narrower in scope than the services governing biomedical research, comparison to existing internet-based platforms, like Airbnb, can be informative.

The "melanoma-enriched" microRNA miR-4731-5p acts as a tumour suppressor.

We previously identified miR-4731-5p (miR-4731) as a melanoma-enriched microRNA following comparison of melanoma with other cell lines from solid malignancies. Additionally, miR-4731 has been found in serum from melanoma patients and expressed less abundantly in metastatic melanoma tissues from stage IV patients relative to stage III patients. As miR-4731 has no known function, we used biotin-labelled miRNA duplex pull-down to identify binding targets of miR-4731 in three melanoma cell lines (HT144, MM96L and MM253).