Factors Influencing in Vivo Disposition of Polymeric Micelles on Multiple Administrations

l-lactic acid)₃₀ (AB-type), which accumulates in solid tumors through the enhanced permeability and retention (EPR) effect. However, lactosome on multiple administrations changed its pharmacokinetics from accumulation in tumors to liver due to the production of antilactosome IgM, which was triggered by the first administration. This phenomenon is called the accelerated blood clearance (ABC). In order to reduce the production of antilactosome IgM, a novel nanoparticle composed of (poly(sarcosine)₂₃)₃-block-poly(l-lactic acid)₃₀ (A₃B-type) was prepared. The A₃B-type lactosome at the second administration showed an in vivo disposition similar to that at the first administration due to suppression of antibody production. This study involving the AB- and A₃B-type lactosomes, with variation of conditions, revealed that the high local density of poly(sarcosine) chains of the A₃B-type lactosome should relate to the prevention of a polymeric micelle from interacting B-cell receptors.     

A novel missense variant in RBM10 can cause a mild form of TARP syndrome with developmental delay and dysmorphic features

RBM10, is an RNA binding protein that is important for development by regulating the expression of multiple genes. RBM10 is on the X chromosome, and nonsense and frameshift RBM10 variants cause TARP syndrome in males. In a 4-year-old male, we identified a novel maternally inherited missense RBM10 variant in the RRM2 RNA binding domain, c.965C>T, p.Pro322Leu. His clinical features included intellectual disability, developmental delay, growth restriction, hypotonia, and craniofacial malformations. These features were much milder than those described in previously reported cases of TARP syndrome. By in vitro assays, we found that the mutant p.Pro322Leu RBM10 protein retained its specific RNA binding capacity, while gaining a low-affinity nonspecific RNA binding. It was normally localized to the nucleus, but its expression level was significantly reduced with a significantly short half-life. These results indicated that the p.Pro322Leu missense variant causes a developmental disorder in humans through a unique loss-of-function mechanism.     

Diagnostic utility of programmed cell death ligand 1 (clone SP142) immunohistochemistry for malignant lymphoma and lymphoproliferative disorders: A brief review

The programmed cell death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumor cell escape from immune control and has been most extensively investigated for therapeutic purposes. However, PD-L1 immunohistochemistry is still not used widely for diagnosis. We review the diagnostic utility of PD-L1 (by clone SP142) immunohistochemistry in large-cell lymphomas, mainly consisting of classic Hodgkin lymphoma (CHL) and diffuse large B-cell lymphoma (DLBCL). Neoplastic PD-L1 (nPD-L1) expression on Hodgkin and Reed-Sternberg cells is well-established among prototypic CHL. Of note, EBV+ CHL often poses a challenge for differential diagnosis from peripheral T-cell lymphoma with EBV+ non-malignant large B-cells; their distinction is based on the lack of PD-L1 expression on large B-cells in the latter. The nPD-L1 expression further provides a good diagnostic consensus for CHL with primary extranodal disease conceivably characterized by a combined pathogenesis of immune escape of tumor cells and immunodeficiency. Compared with CHL, the nPD-L1 expression rate is much lower in DLBCL, highlighting some specific subgroups of intravascular large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and EBV+ DLBCL. They consist of nPD-L1-positive and -negative subgroups, but their clinicopathological significance remains to be elucidated. Microenvironmental PD-L1 positivity on immune cells may be associated with a favorable prognosis in extranodal DLBCL. PD-L1 (by SP142) immunohistochemistry has helped us to understand the immune biology of lymphoid neoplasms possibly related by immune escape and/or immunodeficiency. However, knowledge of these issues remains limited and should be clarified for diagnostic consensus in the future.     

A Long-term Persistent Vascular Fluorodeoxyglucose Uptake in a Patient with Large-vessel Vasculitis

We herein report a case of large-vessel vasculitis in a 57-year-old woman who developed an intermittent fever and weight loss. While contrast-enhanced computed tomography was noncontributory, positron emission tomography-computed tomography (PET-CT) revealed the diffuse, intense uptake of fluorodeoxyglucose (FDG) in the aorta and its branches. Although she had no signs of relapse after successful oral corticosteroid therapy, PET-CT at 30 months revealed a persistent FDG uptake in the large vessels, which warranted regular follow-up imaging for vascular complications. In cases with an intense FDG uptake at the diagnosis, PET-CT follow-up after clinical remission may help predict the risk of relapse and vascular complications.     

Extracts of Musa basjoo induce growth inhibition and changes in the protein expression of cell cycle control molecules in human colorectal cancer cell lines

Musa basjoo (MB) is a species of the banana plant belonging to the genus Musa that has been used as a folk medicine. However, evidence-based biological activities and the molecular mechanism of action of MB are unknown. Thus, the aim of the present study was to examine whether the crude dried leaf extracts of MB inhibit the growth of colorectal (HT29 and HCT116) and other types (HepG2, MCF-7 and PC-3) of human cancer cell lines. Crude extracts of MB inhibited the growth of cells with IC₅₀ values of 136 µg/ml (acetone extract, HT29), 51 µg/ml (acetone extract, HCT116), 45 µg/ml (acetone extract, HepG2), 40 µg/ml (acetone extract, MCF-7), 29 µg/ml (acetone extract, PC-3), 175 µg/ml (methanol extract, HT29), 137 µg/ml (methanol extract, HCT116), 102 µg/ml (methanol extract, HepG2), 85 µg/ml (methanol extract, MCF-7), and 85 µg/ml (methanol extract, PC-3) in colony formation assays, and 126 µg/ml (acetone extract, HT29), 68 µg/ml (acetone extract, HCT116), 260 µg/ml (methanol extract, HT29), and 216 µg/ml (methanol extract, HCT116) in MTT assays. Thin layer chromatography analysis revealed the potential existence of aromatic compounds in the acetone extract of MB. Flow cytometric analysis indicated that the percentage of cells in G1 increased, and this was associated with a concomitant decrease of cells in the S and/or G2-M phases of the cell cycle. When colorectal cancer cells were treated with acetone extract of MB, there was a marked decrease in the levels of expression of the cyclin D1, cyclin E, cdk2 and cdk4 proteins and a marked increase in the levels of the expression of the p21^CIP1, p27^KIP1, and p53 proteins, but those of apoptosis-associated protein PARP did not change. There was a tendency for acetone extract of MB to inhibit xenograft tumor growth in mice. Collectively, the crude extracts of MB contain active components that exert growth inhibition of human cancer cells. This is the first systematic study of the anticancer activity of MB and may broaden insights into the possible clinical approach of specific herbal medicines.     

An Earlier First Meal Timing Associates with Weight Loss Effectiveness in A 12-Week Weight Loss Support Program

Recent studies have reported that meal timing may play an important role in weight regulation, however it is unknown whether the timing of meals is related to the amount of weight loss. This study aimed to examine the relationship between indices of meal timing and weight loss during weight loss intervention in adults. A 12-week weight loss support program was conducted for 97 adults (age: 47.6 ± 8.3 years, BMI: 25.4 ± 3.7 kg/m²). After the program, body weight decreased by −3.0 ± 2.7%. Only the start of the eating window was positively correlated with the weight change rate in both sexes (men: r = 0.321, p = 0.022; women: r = 0.360, p = 0.014). The participants were divided into two groups based on the start of the eating window as follows: the early group (6:48 ± 0:21 AM) and the late group (8:11 ± 1:05 AM). The weight loss rate in the early group was significantly higher (−3.8 ± 2.7%) than that in the late group (−2.2 ± 2.5%). The present results showed that the start of the early eating window was associated with weight loss and suggested paying attention to meal timing when doing weight loss.     

Effect of Low‐Density Lipoprotein Apheresis for Nephrotic Idiopathic Membranous Nephropathy as Initial Induction Therapy

Low‐density lipoprotein apheresis (LDL‐A) has been used for nephrotic syndrome (NS) caused by focal segmental glomerulosclerosis in Japan. Idiopathic membranous nephropathy (iMN) can also cause treatment‐resistant NS. Therefore, we investigated the effect of LDL‐A during initial induction for it. This retrospective, observational, and single‐center study enrolled consecutive iMN patients who received steroids from March 2000 to May 2015. We compared data between 11 patients treated with LDL‐A (LDL‐A group) and 27 patients without (non‐LDL‐A group) at baseline and 4 and 8 weeks later. Reduction rate of proteinuria and increase rate of serum albumin in LDL‐A group were significantly higher than the other after 4 weeks (P = 0.036 and 0.030) and 8 weeks (P = 0.030 and <0.001), respectively. There was no adverse event caused by LDL‐A and immunosuppressant dose was not significantly different. In conclusion, LDL‐A may be an effective choice for initial induction of nephrotic iMN.