PEGylated liposomes (PL) lose their long-circulating characteristic when
administered repeatedly, called the accelerated blood clearance (ABC)
phenomenon. A PEG lipid with a maleimide (MAL) group at the PEG terminal, MAL-PEG-DSPE,
is used in various studies as a linker for ligand-bound liposomes such as
antibody-modified liposomes. However, most ABC phenomenon research used PL with
a terminal methoxy group. In this study, authors prepared MAL-PEG-DSPE
liposomes (PL-MAL) to evaluate the effect of PL-MAL on the ABC phenomenon
induction. These findings indicate PL-MAL induced the ABC phenomenon
independent of the production of IgM antibodies against PEG. This study
provides valuable findings for further studies using ligand-bound liposomes.
eruption caused by anti-epidermal growth factor receptor (EGFR) antibodies such
as panitumumab reduces treatment adherence and patient quality of life; an
alternative therapy is desired. Although the mechanism underlying acne-like
eruption associated with anti-EGFR antibody remains unclear, previous studies
have suggested that the inhibition of cyclooxygenase (COX)-2 is effective to
acne-like eruption caused by low-molecular-weight EGFR inhibitors such as
erlotinib. Authors aimed to investigate whether the concurrent use of oral
Non-steroidal Anti-inflammatory Drugs (NSAIDs) and EGFR antibodies and
presented preliminary evidence that oral NSAIDs may help prevent acne-like
eruptions caused by panitumumab.
Esmolol, an antedrug, is clinically used for long period due to its
rapid onset of action and elimination at a rate greater than cardiac output.
The authors found the esterases involved in the hydrolysis of esmolol. Esmolol was
hydrolyzed by human carboxylesterase 1 (hCE1) in leukocytes and platelets. The
human hepatic clearance limited by hepatic blood flow was obtained by
microsomal hydrolysis by hCE1 and cytosolic hydrolysis by acyl protein
thioesterase 1 (APT1). The
expression of hCE1 and APT1 in human lung might cause the high total clearance
of esmolol, which is 3.5-fold greater than cardiac output.
Y, et al. have already reported that N-(4-Hydroxyphenyl)-retinamide (4-HPR)
inhibits dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity, and
suppresses SARS-CoV-2 infection. Here, the authors describe the generation of
DEGS1 knockout VeroE6/TMPRSS2 cells and their use to evaluate the infectivity
and the effect of 4-HPR on SARS-CoV-2 infection. This study reports that DEGS1
is not involved in SARS-CoV-2 infection, including viral replication and the
release of viral progeny. Further investigation is needed to elucidate the
exact mechanism underlying the inhibition in SARS-CoV-2 infection by 4-HPR.
4-HPR has been extensively studied for cancer treatment. Therefore, the results
of this study, along with accumulated clinical data on the safety of 4-HPR, are
potential candidates for the treatment of COVID-19.
secrete large numbers of small extracellular vesicles (sEVs). These vesicles
are derived from intraluminal vesicles (ILVs) and contribute to cancer
progression by forming the tumor microenvironment. In this study, Mitani et al.
demonstrated a novel role for SNAP23 in Src-dependent EV secretion: in
Src-transfected cells, SNAP23 translocates to non-rafts and causes cholesterol
depletion, resulting in the upregulation of ILV. They also found that pancreatic cancer
patients with high SNAP23 expression have a poor prognosis. These findings
suggest that the Src-SNAP23-sEV axis contributes to cancer progression.