Artemisinin (ART) dimers show potent anti-proliferative activities against breast cancer cells. To facilitate their clinical development, novel pH-responsive artemisinin dimers were synthesized for liposomal nanoparticle formulations. A new ART dimer was designed to become increasingly water-soluble as pH declines. The new artemisinin dimer piperazine derivatives (ADPs) remained tightly associated with liposomal nanoparticles (NPs) at neutral pH but were efficiently released at acidic pH's that are known to exist within solid tumors and organelles such as endosomes and lysosomes. ADPs incorporated into nanoparticles down regulated the anti-apoptotic protein, survivin, and cyclin D1 when incubated at low concentrations with breast cancer cell lines. We demonstrate for the first time, for any ART derivative, that ADP NPs can down regulate the oncogenic protein HER2, and its counterpart, HER3 in a HER2+ cell line. We also show that the wild type epidermal growth factor receptor (EGFR or HER1) declines in a triple negative breast cancer (TNBC) cell line in response to ADP NPs. The declines in these proteins are achieved at concentrations of NP109 at or below 1 µM. Furthermore, the new artemisinin derivatives showed improved cell-proliferation inhibition effects compared to known dimer derivatives.
Objectives
To investigate what findings are new on contrast-enhanced abdominopelvic CT in patients infected with SARS-CoV-2.
Methods
Contrast-enhanced CT of the abdomen and pelvis of patients with COVID-19 at a tertiary oncologic center acquired over a 2-month period were reviewed independently by two readers and scored for new imaging abnormalities compared with a prior scan. CT scans were included if the study was performed between − 3 and 45 days from the time of COVID-19 diagnosis. Clinical information was gathered from the medical records.
Results
A total of 63 patients (34 male, 29 female; mean age 60.6 years, range 24.4–85.0 years) were included in this retrospective cross-sectional study. Aside from new ground glass opacities seen at the lung bases (29/63, 46.0%), the most common findings were new thickening of the stomach, small bowel or colon or fluid-filled colon (14/63, 22.2%), new small volume ascites (7/63, 14.3%), gallbladder distention in those without prior cholecystectomy (3/43, 7.0%), and single cases each of acute pancreatitis (1/63, 1.6%) as well as new portal vein thrombosis (1/63, 1.6%).
Conclusion
Aside from lung base ground glass opacities, the most common new imaging abnormality on abdominopelvic CT in patients with COVID-19 finding in our cohort was abnormalities of the gastrointestinal tract, followed by small volume ascites, gallbladder distention, and isolated cases of pancreatitis and portal vein thrombosis. These findings overlap with those previously reported that did not have a prior scan for comparison, and provide supportive evidence that some of these findings may be related to SARS-CoV-2 infection.
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