A novel methylated cell-free DNA marker panel to monitor treatment response in metastatic prostate cancer.

This study examined circulating cell-free DNA (cfDNA) biomarkers associated with androgen treatment resistance in metastatic castration resistance prostate cancer (mCRPC). We designed a panel of nine candidate cfDNA methylation markers using droplet digital PCR (Methyl-ddPCR) and assessed methylation levels in sequentially collected cfDNA samples from patients with mCRPC. Increased cfDNA methylation in eight out of nine markers during androgen-targeted treatment correlated with a faster time to clinical progression.

Investigating Urinary Circular RNA Biomarkers for Improved Detection of Renal Cell Carcinoma.

Renal cell carcinomas (RCC) are usually asymptomatic until late stages, posing several challenges for early detection of malignant disease. Non-invasive liquid biopsy biomarkers are emerging as an important diagnostic tool which could aid with routine screening of RCCs. Circular RNAs (circRNAs) are novel non-coding RNAs that play diverse roles in carcinogenesis.

Distinct DNA methylation patterns associated with treatment resistance in metastatic castration resistant prostate cancer.

Androgens are a major driver of prostate cancer (PCa) and continue to be a critical treatment target for advanced disease, which includes castration therapy and antiandrogens. However, resistance to these therapies leading to metastatic castration-resistant prostate cancer (mCRPC), and the emergence of treatment-induced neuroendocrine disease (tNEPC) remains an ongoing challenge. Instability of the DNA methylome is well established as a major hallmark of PCa development and progression.

Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment.

We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression.

Impaired resolution of inflammation in the Endoglin heterozygous mouse model of chronic colitis.

Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng (+/-)) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and pathological angiogenesis. We now report that colitic Eng (+/-) mice have low colonic levels of active TGF-β1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-β1.

Anti-VEGF therapy reduces intestinal inflammation in Endoglin heterozygous mice subjected to experimental colitis.

Chronic intestinal inflammation is associated with pathological angiogenesis that further amplifies the inflammatory response. Vascular endothelial growth factor (VEGF), is a major angiogenic cytokine that has been implicated in chronic colitis and inflammatory bowel diseases. Endoglin (CD105), a transforming growth factor-β superfamily co-receptor expressed on endothelial and some myeloid cells, is a modulator of angiogenesis involved in wound healing and potentially in resolution of inflammation.

Endoglin and activin receptor-like kinase 1 heterozygous mice have a distinct pulmonary and hepatic angiogenic profile and response to anti-VEGF treatment.

Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia associated with dysregulated angiogenesis and arteriovascular malformations. The disease is caused by mutations in endoglin (ENG; HHT1) or activin receptor-like kinase 1 (ALK1; HHT2) genes, coding for transforming growth factor β (TGF-β) superfamily receptors. Vascular endothelial growth factor (VEGF) has been implicated in HHT and beneficial effects of anti-VEGF treatment were recently reported in HHT patients.

Dextran sulfate sodium leads to chronic colitis and pathological angiogenesis in Endoglin heterozygous mice.

Background: Pathological angiogenesis is an intrinsic component of chronic intestinal inflammation, which results in remodeling and expansion of the gut microvascular bed. Endoglin is essential for endothelial cell function and physiological angiogenesis. In this study we investigated its potential role in the regulation of inflammation by testing the response of Endoglin heterozygous (Eng(+/-)) mice to experimental colitis.