Circulating tumour cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies.

Objective: Most of the work in terms of liquid biopsies in patients with solid tumors is focused on circulating tumor DNA (ctDNA). Our aim was to evaluate the feasibility of using circulating tumor cells (CTCs) in peripheral blood samples from patients with advanced or metastatic gastrointestinal (GI) cancers. Methods: In this prospective study, blood samples were collected from each patient in 2 AccuCyte® blood collection tubes and each tube underwent CTC analysis performed utilizing the RareCyte® platform. The results from both tubes were averaged and a total of 150 draws were done, with 281 unique reported results. The cadence of sampling was based on convenience sampling and piggybacked onto days of actual clinical follow-ups and treatment visits. The CTC results were correlated with patient- and tumor-related variables. Results: Data from a total of 59 unique patients were included in this study. Patients had a median age of 58 years, with males representing 69% of the study population. More than 57% had received treatment prior to taking blood samples. The type of GI malignancy varied, with more than half the patients having colorectal cancer (CRC, 54%) followed by esophageal/gastric cancer (17%). The least common cancer was cholangiocarcinoma (9%). The greatest number of CTCs were found in patients with colorectal cancer (Mean: 15.8 per 7.5 ml; Median: 7.5 per 7.5 ml). In comparison, patients with pancreatic cancer (PC) had considerably fewer CTCs (Mean: 4.2 per 7.5 ml; Median: 3 per 7.5 ml). Additionally, we found that patients receiving treatment had significantly fewer CTCs than patients who were not receiving treatment (Median 2.7 versus 0.7). CTC numbers showed noteworthy disparities between patients with responding/stable disease in comparison to those with untreated/progressive disease (Median of 2.7 versus 0). When CTCs were present, biomarker analyses of the four markers human epidermal growth factor receptor 2 (HER2)/programmed death-ligand 1 (PD-L1)/Kiel 67 (Ki-67)/epidermal growth factor receptor (EGFR) was feasible. Single cell sequencing confirmed the tumor of origin. Conclusion: Our study is one of the first prospective real-time studies evaluating CTCs in patients with GI malignancies. While ctDNA-based analyses are more common in clinical trials and practice, CTC analysis provides complementary information from a liquid biopsy perspective that is of value and worthy of continued research.

False-Positive Liquid Biopsy Assays Secondary to Overlapping Aberrant Methylation from Non-Cancer Disease States.

Introduction: Liquid biopsies are increasingly being adopted in the care of patients with cancer. Not only in patients with metastatic disease but the utility is also being recognized in earlier phases of the journey of a patient with cancer. More recently, methylated platforms are offering another lens of looking at the same question more so in minimal residual disease (MRD) and early detection settings. While false positives secondary to clonal hematopoiesis of indeterminate potential (CHIP) are recognized as one entity to consider when interpreting these assays, and advanced CHIP filtering bioinformatics platforms can prevent this, false positives secondary to aberrant methylation are not described. Case Presentation: Herein, we report a case of a patient with hepatitis C-related viremia and a very high viral load that had a false-positive plasma-only colorectal MRD assay. The colorectal MRD assay spontaneously cleared on hepatitis C virus therapy which led to clearance of the virus. Conclusion: As these assays are increasingly applied in real-world settings, it would be of value to consider non-cancer chronic disease states that may lead to aberrant methylation that could lead to a false-positive assay.

Larotrectinib in Mismatch-Repair-Deficient TRK Fusion-Positive Metastatic Colon Cancer After Progression on Immunotherapy.

A 43-year-old woman presented with recurrent metastatic colon cancer with metastases to the peritoneum after having initially been diagnosed with stage IIB colon cancer and deferring adjuvant chemotherapy. Circulating tumor DNA (ctDNA)-based liquid biopsy testing revealed microsatellite instability-high (MSI-H) status, which was also confirmed on tissue testing. This patient then underwent four cycles of pembrolizumab and two cycles of ipilimumab and nivolumab (CTLA-4 rescue) with, unfortunately, progression of the disease. The patient was subsequently treated with larotrectinib, given the findings of TRK fusion-positive cancer on next-generation sequencing (NGS), and she was able to undergo curative surgery two months later that showed complete pathologic response. She continues to have no evidence of disease years later as well as no detectable ctDNA on NGS as well as tumor-informed minimal residual disease platforms. This case represents a marked and durable response to larotrectinib in a patient with deficiency in mismatch repair/MSI-H metastatic colorectal cancer harboring an NTRK fusion, bringing to light the potential for use of larotrectinib in earlier treatment lines in patients, and/or choice of targeted therapy versus immunotherapy in this patient subset.

Structure optimization of perovskite quantum dot light-emitting diodes.

Although all-inorganic perovskite light emitting diodes (PeLED) have satisfactory stability under an ambient atmosphere, producing devices with high performance is challenging. A device architecture with a reduced energy barrier between adjacent layers and optimized energy level alignment in the PeLED is critical to achieve high electroluminescence efficiency. In this study, we report the optimization of a CsPbBr3-based PeLED device structure with Li-doped TiO2 nanoparticles as the electron transport layer (ETL). Optimal Li doping balances charge carrier injection between the hole transport layer (HTL) and ETL, leading to superior performance in both devices. The turn-on voltages for devices with Li-doped TiO2 nanoparticles were significantly reduced from 7.7 V to 4.9 V and from 3 V to 2 V in the direct and inverted PeLED structures, respectively. The low turn-on voltage for green emission is one of the lowest values among the reported CsPbBr3-based PeLEDs. Further investigations show that the device with an inverted structure is superior to the device with a direct structure because the energy barrier for carrier injection was minimized. The inverted structure devices exhibited a current efficiency of 5.6 cd A-1 for the pristine TiO2 ETL, while it was 15.2 cd A-1 for the Li-doped TiO2 ETL, a factor of ∼2.7 enhancement at 5000 cd m-2.

Toxicity of PEG-Coated CoFe2O4 Nanoparticles with Treatment Effect of Curcumin.

In this work, CoFe2O4 nanoparticles coated with polyethylene glycol (PEG) were successfully synthesized via a hydrothermal technique. Morphological studies of the samples confirmed the formation of polycrystalline pure-phase PEG-CoFe2O4 nanoparticles with sizes of about 24 nm. Toxicity induced by CoFe2O4 nanoparticles was investigated, and biological assays were performed to check the toxicity effects of CoFe2O4 nanoparticles. Moreover, the healing effect of toxicity induced in living organisms was studied using curcumin and it was found that biochemical indexes detoxified and improved to reach its normal level after curcumin administration. Thus, PEG-coated CoFe2O4 synthesized through a hydrothermal method can be utilized in biomedical applications and curcumin, which is a natural chemical with no side effects, can be used for the treatment of toxicity induced by the nanoparticles in living organisms.

Surface Modification and Damage of MeV-Energy Heavy Ion Irradiation on Gold Nanowires.

Gold nanowires with diameters ranging from 20 to 90 nm were fabricated by the electrochemical deposition technique in etched ion track polycarbonate templates and were then irradiated by Xe and Kr ions with the energy in MeV range. The surface modification of nanowires was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterizations. Different craters with and without protrusion on the gold nanowires were analyzed, and the two corresponding formation mechanisms, i.e., plastic flow and micro-explosion, were investigated. In addition, the sputtered gold nanoparticles caused by ion irradiation were studied and it was confirmed that the surface damage produced in gold nanowires was increased as the diameter of the nanowires decreased. It was also found that heavy ion irradiation can also create stacking fault tetrahedrons (SFTs) in gold nanowires and three different SFTs were confirmed in irradiated nanowires. A statistical analysis of the size distribution of SFTs in gold nanowires proved that the average size distribution of SFT was positively related to the nuclear stopping power of incident ions, i.e., the higher nuclear stopping power of incident ions could generate SFT with a larger average size in gold nanowires.

Temperature- and Angle-Dependent Magnetic Properties of Ni Nanotube Arrays Fabricated by Electrodeposition in Polycarbonate Templates.

Parallel arrays of Ni nanotubes with an external diameter of 150 nm, a wall thickness of 15 nm, and a length of 1.2 ± 0.3 µm were successfully fabricated in ion-track etched polycarbonate (PC) templates by electrochemical deposition. The morphology and crystal structure of the nanotubes were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Structural analyses indicate that Ni nanotubes have a polycrystalline structure with no preferred orientation. Angle dependent hysteresis studies at room temperature carried out by using a vibrating sample magnetometer (VSM) demonstrate a transition of magnetization between the two different magnetization reversal modes: curling rotation for small angles and coherent rotation for large angles. Furthermore, temperature dependent magnetic analyses performed with a superconducting quantum interference device (SQUID) magnetometer indicate that magnetization of the nanotubes follows modified Bloch's law in the range 60-300 K, while the deviation of the experimental curve from this law below 60 K can be attributed to the finite size effects in the nanotubes. Finally, it was found that coercivity measured at different temperatures follows Kneller's law within the premises of Stoner-Wohlfarth model for ferromagnetic nanostructures.

Controlled crystallinity and crystallographic orientation of Cu nanowires fabricated in ion-track templates.

The hallmark of materials science is the ability to tailor the structures of a given material to provide a desired response. In this work, the structures involving crystallinity and crystallographic orientation of Cu nanowires electrochemically fabricated in ion-track templates have been investigated as a function of fabrication condition. Both single crystalline and polycrystalline nanowires were obtained by adjusting applied voltages and temperatures of electrochemical deposition. The anti-Hall-Petch effect was experimentally evidenced in the polycrystalline nanowires. The dominant crystallographic orientations of wires along [111], [100], or [110] directions were obtained by selecting electrochemical deposition conditions, i.e., H(2)SO(4) concentration in electrolyte, applied voltage, and electrodeposition temperature.