Tumour budding as a prognostic biomarker in biopsies and resections of neoadjuvant-treated rectal adenocarcinoma.

Background: Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment.

Methods And Results: A single-centre, retrospective cohort study was conducted.

Relevance of shrinkage versus fragmented response patterns in rectal cancer.

Aims: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.

Methods And Results: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response.

Improving tumor budding reporting in colorectal cancer: a Delphi consensus study.

Tumor budding is a long-established independent adverse prognostic marker in colorectal cancer, yet methods for its assessment have varied widely. In an effort to standardize its reporting, a group of experts met in Bern, Switzerland, in 2016 to reach consensus on a single, international, evidence-based method for tumor budding assessment and reporting (International Tumor Budding Consensus Conference [ITBCC]). Tumor budding assessment using the ITBCC criteria has been validated in large cohorts of cancer patients and incorporated into several international colorectal cancer pathology and clinical guidelines.

Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

Histological 'phenotypic subtypes' that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I-III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy.

Blood-brain barrier dysfunction in a boxer with chronic traumatic encephalopathy and schizophrenia.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition characterized by the perivascular deposition of phosphorylated τ (p-τ) protein aggregates resulting from repetitive mild traumatic brain injury (rTBI). Advances in the field have revealed the significance of repetitive head trauma in the pathogenesis of CTE in contact sports as well as military veterans. In this study we provide evidence of blood-brain barrier (BBB) disruption in regions of intense perivascular p-τ deposition in a former professional boxer diagnosed with CTE and schizophrenia.

Parallel mRNA, proteomics and miRNA expression analysis in cell line models of the intestine.

Aim: To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine.

Methods: Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.

Matrix metalloproteinase processing of PTHrP yields a selective regulator of osteogenesis, PTHrP.

Parathyroid hormone-related protein (PTHrP) is a critical regulator of bone resorption and augments osteolysis in skeletal malignancies. Here we report that the mature PTHrP hormone is processed by matrix metalloproteinases to yield a stable product, PTHrP. PTHrP retains the ability to signal through PTH1R to induce calcium flux and ERK phosphorylation but not cyclic AMP production or CREB phosphorylation.

The prognostic utility of the transcription factor SRF in docetaxel-resistant prostate cancer: in-vitro discovery and in-vivo validation.

Background: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists.

Manipulating MiRNA Expression to Uncover Hidden Functions.

There are a numerous target prediction algorithms that allow users to identify putative targets of their microRNAs (miRNAs) of interest. Although these tools are useful to gain insight into the potential role of miRNAs in regulating cellular processes, physical manipulation of the expression of the miRNA is the most superior way to truly determine the function of the miRNA in the system of interest. This chapter outlines methods to reveal miRNA function by modulating miRNA expression by transient transfection of miRNA mimics and inhibitors, and stable overexpression and reduction of miRNA expression using plasmid overexpression and sponge vectors.

Altered expression of mir-222 and mir-25 influences diverse gene expression changes in transformed normal and anaplastic thyroid cells, and impacts on MEK and TRAIL protein expression.

Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer-related deaths each year. Our group and others have previously demonstrated dysfunctional microRNA (miRNA or miR) expression in the context of thyroid cancer. The objective of the present study was to investigate the impact of synthetic manipulation of expression of miR-25 and miR-222 in benign and malignant thyroid cells.

Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression.

Background: Screening for the early detection of colorectal cancer is important to improve patient survival. The aim of this study was to investigate the potential of circulating cell-free miRNAs as biomarkers of CRC, and their efficiency at delineating patients with polyps and benign adenomas from normal and cancer patient groups.

Methods: The expression of 667 miRNAs was assessed in a discovery set of 48 plasma samples comprising normal, polyp, adenoma, and early and advanced cancer samples.

A simplified method to recover urinary vesicles for clinical applications, and sample banking.

Urinary extracellular vesicles provide a novel source for valuable biomarkers for kidney and urogenital diseases: Current isolation protocols include laborious, sequential centrifugation steps which hampers their widespread research and clinical use. Furthermore, large individual urine sample volumes or sizable target cohorts are to be processed (e.g.

Comparative transcriptomic analysis of cultivated limbal epithelium and donor corneal tissue reveals altered wound healing gene expression.

Purpose: The improved surgical outcomes associated with transplantation of cultivated amniotic membrane expanded limbal epithelium (AMLE) compared to traditional donor methods has led to substantial adoption of this technique for treatment of limbal stem cell deficiency.

Methods: The mRNA expression profiles of AMLE and CE were assayed using microarrays. Transcripts with a 1.

BreastMark: an integrated approach to mining publicly available transcriptomic datasets relating to breast cancer outcome.

Introduction: Breast cancer is a complex heterogeneous disease for which a substantial resource of transcriptomic data is available. Gene expression data have facilitated the division of breast cancer into, at least, five molecular subtypes, namely luminal A, luminal B, HER2, normal-like and basal. Once identified, breast cancer subtypes can inform clinical decisions surrounding patient treatment and prognosis.

A gene expression profile indicative of early stage HER2 targeted therapy response.

Background: Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies.

MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.

MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27(KIP) and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1.

Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis.

Weighted gene coexpression network analysis (WGCNA) is a powerful 'guilt-by-association'-based method to extract coexpressed groups of genes from large heterogeneous messenger RNA expression data sets. We have utilized WGCNA to identify 11 coregulated gene clusters across 2342 breast cancer samples from 13 microarray-based gene expression studies. A number of these transcriptional modules were found to be correlated to clinicopathological variables (e.

Transcriptomic analysis of clonal growth rate variation during CHO cell line development.

The selection of clones displaying a high rate of cell growth is an essential component of Chinese hamster ovary (CHO) cell line development. In recent years various "omics" technologies have been utilised to understand the mechanisms underlying bioprocess phenotypes. In this study, gene expression analysis using a CHO-specific microarray was conducted for a panel of CHO-K1 MAb-secreting cell lines spanning a range of growth rates that were derived from a single cell line development project.

Integrated miRNA, mRNA and protein expression analysis reveals the role of post-transcriptional regulation in controlling CHO cell growth rate.

Background: To study the role of microRNA (miRNA) in the regulation of Chinese hamster ovary (CHO) cell growth, qPCR, microarray and quantitative LC-MS/MS analysis were utilised for simultaneous expression profiling of miRNA, mRNA and protein. The sample set under investigation consisted of clones with variable cellular growth rates derived from the same population. In addition to providing a systems level perspective on cell growth, the integration of multiple profiling datasets can facilitate the identification of non-seed miRNA targets, complement computational prediction tools and reduce false positive and false negative rates.

Gene expression changes as markers of early lapatinib response in a panel of breast cancer cell lines.

Background: Lapatinib, a tyrosine kinase inhibitor of HER2 and EGFR and is approved, in combination with capecitabine, for the treatment of trastuzumab-refractory metastatic breast cancer. In order to establish a possible gene expression response to lapatinib, a panel of breast cancer cell lines with varying sensitivity to lapatinib were analysed using a combination of microarray and qPCR profiling.

Methods: Co-inertia analysis (CIA), a data integration technique, was used to identify transcription factors associated with the lapatinib response on a previously published dataset of 96 microarrays.

Olfactomedin III expression contributes to anoikis-resistance in clonal variants of a human lung squamous carcinoma cell line.

Three clonal subpopulations of DLKP, a poorly differentiated squamous lung carcinoma cell line, display striking differences in ability to survive in suspension (anoikis resistance). DLKP-SQ is anoikis resistant (7.5% anoikis at 24 h).

Carotenoid content of commonly consumed herbs and assessment of their bioaccessibility using an in vitro digestion model.

Herbs are a rich source of bioactive phytochemicals such as carotenoids, which are known to exert various positive biological effects. However, there is very limited information in the literature regarding the content and bioavailability of carotenoids from commonly consumed herbs. Therefore, the objectives of the present study were first, to determine the carotenoid content of eight herbs namely basil (Ocimum basilicum), coriander (Coriandrum sativum), dill (Anethum graveolens), mint (Metha L.

Bioaccessibility, uptake, and transport of carotenoids from peppers (Capsicum spp.) using the coupled in vitro digestion and human intestinal Caco-2 cell model.

Spanish bell peppers (Capsicum annuum L.) and chili peppers sourced from Kenya and Turkey were analyzed for their carotenoid content, bioaccessibility, and bioavailability. The order of total carotenoid content in peppers and their respective micelles was red > green > yellow.

Bioactive properties of wood knot extracts on cultured human cells.

Not all felled wood is converted to timber or pulp, with the remaining material being a rich source of relatively unexplored and unexploited potentially novel bioactive compounds. Therefore the potential bioactive effects of two softwood knot (the part of the branch encased in the tree stem) extracts--namely, Pinus banksiana Lamb. (Jack pine) and Picea sitchensis (Bong.