Circulating Tumor Cell Subpopulations Predict Treatment Outcome in Pancreatic Ductal Adenocarcinoma (PDAC) Patients.

There is a high clinical unmet need to improve outcomes for pancreatic ductal adenocarcinoma (PDAC) patients, either with the discovery of new therapies or biomarkers that can track response to treatment more efficiently than imaging. We report an innovative approach that will generate renewed interest in using circulating tumor cells (CTCs) to monitor treatment efficacy, which, in this case, used PDAC patients receiving an exploratory new therapy, poly ADP-ribose polymerase inhibitor (PARPi)-niraparib-as a case study. CTCs were enumerated from whole blood using a microfluidic approach that affinity captures epithelial and mesenchymal CTCs using anti-EpCAM and anti-FAPα monoclonal antibodies, respectively. These antibodies were poised on the surface of two separate microfluidic devices to discretely capture each subpopulation for interrogation. The isolated CTCs were enumerated using immunophenotyping to produce a numerical ratio consisting of the number of mesenchymal to epithelial CTCs (denoted "Φ"), which was used as an indicator of response to therapy, as determined using computed tomography (CT). A decreasing value of Φ during treatment was indicative of tumor response to the PARPi and was observed in 88% of the enrolled patients (n = 31). Changes in Φ during longitudinal testing were a better predictor of treatment response than the current standard CA19-9. We were able to differentiate between responders and non-responders using ΔΦ (p = 0.0093) with higher confidence than CA19-9 (p = 0.033). For CA19-9 non-producers, ΔΦ correctly predicted the outcome in 72% of the PDAC patients. Sequencing of the gDNA extracted from affinity-selected CTC subpopulations provided information that could be used for patient enrollment into the clinical trial based on their tumor mutational status in DNA repair genes.

Evaluation and analysis of perlite and municipal wastewater sludge (biosolids) from three wastewater treatment plants in East Texas, USA.

Municipal wastewater sludge (also known as biosolids) is produced in large quantities from wastewater treatment plants (WWTPs). Traditionally, analyses of biosolids revealed the presence of inorganic (including metals) and organic contaminants which pose health concerns to man and the environment. This study investigated physical-chemical parameters and comparative element concentrations (Ag, Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Mo, Ni, P, Pb, S, Se, Zn, V, Na, S, and P) in biosolids and composted wastewater sludge (CWS) from Nacogdoches Wastewater Treatment Plant (NWWTP), Lufkin Wastewater Treatment Plant (LWWTP), and Angelina-Neches Compost Facility (NCF) in East Texas (USA). In addition, concentrations in perlite, a hydroponic material, were determined via Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy/energy dispersive X-ray diffraction (SEM/EDX), inductively coupled plasma-optical emission spectroscopy (ICP-OES), X-ray diffraction (XRD)), and thermogravimetric (TGA) analysis. Via ICP-OES analysis, metal concentrations in biosolid samples were similar. Macroelement amounts followed the order: NWWS ≈ LWWS > NCS > perlite. Notably, concentrations in biosolids, CWS, and perlite are below recommended USEPA and WHO maximum ceiling levels. The pH of biosolid samples was determined between 5.33 and 6.74. The weight loses of 6-19% wt at ~ 300-700 ℃ are attributed to volatile compounds and inorganic metal oxides. From environmental and circular economy perspectives, this study shows biosolids to be safe, and potential recycling can be encouraged for use in soil amendments. This finding could find impetus to design of much better WWTPs which improve removal efficiencies and encourage recycling of biosolids.