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Biology subjects

Thomas, P. B.

Publications and source records attributed to Thomas, P. B..

3 recordsLinked to original sources

Computationally efficient framework for diagnosing, understanding, and predicting biphasic population growth

Throughout the life sciences, biological populations undergo multiple phases of growth, often referred to as biphasic growth for the commonly-encountered situation involving two phases. Biphasic population growth occurs over a massive range of spatial and temporal scales, ranging from microscopic growth of tumours over several days, to decades-long re-growth of corals in coral reefs that can extend for hundreds of kilometres. Different mathematical models and statistical methods are used to diagnose, understand, and predict biphasic growth. Common approaches can lead to inaccurate predictions of future growth that may result in inappropriate management and intervention strategies being implemented. Here we develop a very general computationally efficient framework, based on profile likelihood analysis, for diagnosing, understanding, and predicting biphasic population growth. The two key components of the framework are: (i) an efficient method to form approximate confidence intervals for the change point of the growth dynamics and model parameters; and, (ii) parameter-wise profile predictions that systematically reveal the influence of individual model parameters on predictions. To illustrate our framework we explore real-world case studies across the life sciences.

systems biology↗

The long non-coding RNA GHSROS reprograms prostate cancer cell lines toward a more aggressive phenotype

It is now appreciated that long non-coding RNAs (lncRNAs) are important players in the orchestration of cancer progression. In this study we characterized GHSROS, a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets. Consistently, transcriptome data revealed that GHSROS alters the expression of cancer-associated genes. Functional analyses in vitro showed that GHSROS mediates tumor growth, migration, and survival and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation of GHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell lines in vitro was recapitulated in a subcutaneous xenograft model. Conversely, in vitro antisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably, GHSROS modulates the expression of PPP2R2C, the loss of which may drive androgen receptor pathway-independent prostate tumor progression in a subset of prostate cancers. Collectively, our findings suggest that GHSROS can reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.

cancer biology↗

No effect of administration of unacylated ghrelin on subcutaneous PC3 xenograft growth in a Rag1-/- mouse model of metabolic dysfunction

Ghrelin is a peptide hormone which, when acylated, regulates appetite, energy balance and a range of other biological processes. Ghrelin predominately circulates in its unacylated form (unacylated ghrelin; UAG). UAG has a number of functions independent of acylated ghrelin, including modulation of metabolic parameters and cancer progression. UAG has also been postulated to antagonise some of the metabolic effects of acyl-ghrelin, including its effects on glucose and insulin regulation. In this study, Rag1-/- mice with high-fat diet-induced obesity and hyperinsulinaemia were subcutaneously implanted with PC3 prostate cancer xenografts to investigate the effect of UAG treatment on metabolic parameters and xenograft growth. Daily intraperitoneal injection of 100 g/kg UAG had no effect on xenograft tumour growth in mice fed normal rodent chow or 23% high-fat diet. UAG significantly improved glucose tolerance in host Rag1-/- mice on a high-fat diet, but did not significantly improve other metabolic parameters. We hypothesise that UAG is not likely to be an effective treatment for prostate cancer, with or without associated metabolic syndrome.\n\nConflict of interestThe authors declare no conflict of interest.

cancer biology↗