No abstract

Summary: The copolymer of N‐isopropylacrylamide and 3‐(acrylamido)phenylboronic acid (82:18, $\overline M _{\rm n}$ = 47 000 g · mol−1) was prepared by free radical polymerization. The copolymer showed typical thermal precipitation behavior in aqueous solutions, its precipitation temperature (TP) being increased from 23 to 32 °C by increasing the pH from 6.5 to 9.7, because of ionization of the phenylboronate units. The pKa was evaluated as 8.9 ± 0.1 from the effect of pH on TP. At pH > 9, i.e., in the anionic form of the copolymer, TP was affected by a very low concentration of glucose (5.6 μM, ΔTP = 1–1.5 °C), because of complex formation with a high binding constant. At a higher concentration of polyols (560 μM, pH > 8) the increase of TP was maximal for the copolymer complexes with fructose (7–10 °C) and decreased in the order: fructose > glucose ≈ mannitol > pentaerythritol > galactose > Tris >glycerol. Di‐ and oligosaccharides (lactose, sucrose, and dextran) caused a slight increase of TP at pH 7.5–8.7 while no effect was observed at pH > 9. Isothermal dissolution of the copolymer suspension in water (27 °C, pH 8.5) was possible in the presence of fructose or mannitol but required higher concentrations (1.4–3.6 × 103 μM) as compared to those which enabled the shift of TP in the soluble copolymer. The dissolution rate increased with fructose concentrations.

ABSTRACT:In this study, we investigated whether pomegranate juice could inhibit CYP2C9 activity. The ability of pomegranate juice to inhibit the diclofenac 4-hydroxylase activity of human CYP2C9 was examined using human liver microsomes. Pomegranate juice was shown to be a potent inhibitor of human CYP2C9. The addition of 25 l (5% v/v) of pomegranate juice resulted in almost complete inhibition of human CYP2C9 activity. In addition, we investigated the effect of pomegranate juice on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. Relative to the control group, the area under the concentration-time curve was approximately 1.2-fold greater when pomegranate juice (3 ml) was injected p.o. 1 h before the p.o. administration of the tolbutamide (20 mg/ kg). The elimination half-life of tolbutamide was not altered by pomegranate juice administration. These results suggest pomegranate juice ingestion inhibits the intestinal metabolism of tolbutamide without inhibiting the hepatic metabolism in rats. Thus, we discovered that pomegranate juice inhibited human CYP2C9 activity and furthermore increased tolbutamide bioavailability in rats.

Crosslinked N-(2-pyridylmethyl)chitosan, N-(2-thienylmethyl)chitosan, and N-[3-(methylthio)propyl]chitosan were newly synthesized. The amino group of the active adsorption site of chitosan was protected by Schiff’s base formation prior to being crosslinked by 2-(chloromethyl)oxirane. The final chitosan derivatives were obtained by reducing the imine moiety of the Schiff’s bases with sodium borohydride. The adsorption behavior of metal ions on the chitosan derivatives was examined from a solution containing hydrochloric acid using a batchwise method. These chitosan derivatives exhibited high selectivities and excellent loading capacities for gold(III), palladium(II), and platinum(IV) over base metals in hydrochloric acid. In order to elucidate the adsorption species of palladium(II) on the chitosan derivatives, the effect of the chloride ion concentration on the distribution ratio in the adsorption of palladium(II) was examined. The adsorption capacities of these chitosan derivatives for palladium(II) were found to be about 2.5—3 times greater than that of the cross-linked original chitosan. The desorption of palladium(II) was performed to an extent of 70% by a single batchwise treatment with aqueous thiourea solution.

Background/Aim: SLC20A1 has been identified as a prognostic marker in ER+ breast cancer. However, the role of SLC20A1 expression in breast cancer subtypes other than the ER+ types remains unclear. Materials and Methods: Genomics datasets were downloaded and analyzed, and the effect of SLC20A1 knockdown using targeted siRNA on cell viability and tumor-sphere formation was assessed. Results: SLC20A1 high patients with ER+, claudin-low or basal-like breast cancers showed poor prognoses. SLC20A1 high patients treated with radiotherapy had poor clinical outcomes. SLC20A1 knockdown suppressed the viability of MDA-MB 231 (claudin-low), MDA-MB 468 (basal-like) and MCF-7 (ER+) cells, and tumor-sphere formation by ALDH1 high cells. These results suggest that SLC20A1 is involved in cancer progression and contributes to clinical outcomes in patients with ER+, claudin-low and basal-like breast cancers. Conclusion: SLC20A1 is a potential prognostic marker and therapeutic target in ER+, claudin-low and basal-like breast cancers.Breast cancer is the most commonly occurring cancer among women worldwide, with 2.1 million new cases (24.2% of all cancers in women) and 0.6 million cancer-related deaths (15.0% of all cancer-related deaths among woman) annually (1). Breast cancer is classified using immunohistochemistry (IHC) and gene expression patterns (PAM50) (2-7). Based on IHC, breast cancer is classified into four types: ER+ and/or PgR+ HER2-type, ER+ and/or PgR+ HER2+ type, ER-and PgR-HER2+ type and triple negative type (TNBC). Based on PAM50, breast cancer is classified into at least six subtypes: normal-like, luminal A, luminal B, HER2-enriched, claudin-low and basal-like (2-7). Among these, the luminal A and luminal B types express ER (8, 9), and some luminal B and HER2-enriched types express HER2 (4, 8-11). Many claudin-low and basal-like types overlap with the TNBC type (6,(12)(13)(14).Breast cancer treatment mainly entails surgery, radiotherapy and drug therapy, which may include chemotherapy, endocrine therapy and/or molecular target therapy. Overall, breast cancer prognosis is good. Endocrine therapy is selected against ER+ type and a HER2-targeted antibody, such as trastuzumab, is used to treat HER2 type (11,15,16). However, there is no effective drug or molecular targeted therapy for TNBC or its overlapping claudin-low and basal-like types. Consequently, those patients are treated only with surgery, radiotherapy and chemotherapy, and have poor prognoses (6,13,(15)(16)(17). Moreover, it is also known that in some of these cases, chemo-and/or radiotherapy actually stimulates cancer progression (18)(19)(20). It is therefore essential to identify effective prognostic markers and molecular targets that can be exploited for the treatment of the claudin-low and basallike breast cancer subtypes.A major hurdle that must be overcome for therapy to be effective against the claudin-low and basal-like subtypes is 43 This article is freely accessible online.