著者

山崎 幹夫 松尾 光芳 柴田 承二

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.13, no.8, pp.1015-1017, 1965-08-25 (Released:2008-03-31)

被引用文献数

16 23

著者

Lili Li Ning Wang Qizhong Jin Qian Wu Yafang Liu Yan Wang

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.65, no.11, pp.1004-1010, 2017-11-01 (Released:2017-11-01)

参考文献数

35

被引用文献数

17 20

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Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classical prescription in traditional Chinese medicine treating blood stagnation in the head and facial channels, especially cerebral ischemia. We investigate the effect of TQHXD on the expressions of related proteins of the blood–brain barrier (BBB) and analysis of constituents in the cerebrospinal fluid (CSF) on cerebral ischemic model rats. Here, we demonstrate that TQHXD protected the hippocampus neurons, reduced the opening of tight junction (TJ) and decreased the permeability of BBB by up-regulating ZO-1, occludin, claudin-5 expressions, down-regulating aquaporin-4 (AQP-4) and matrix metalloproteinase-9 (MMP-9) expressions. Meanwhile, we detected Muscone, ligustilide and hydroxysafflor yellow A in CSF on cerebral ischemic model rats. These compounds could be identified as the main active ingredients of TQHXD on protecting the damaged BBB. These results suggest that TQHXD could act as a potential neuroprotective agent against BBB damage for cerebral ischemia.

著者

Mayumi Nakanishi-Matsui Naomi Matsumoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.10, pp.1426-1431, 2022-10-01 (Released:2022-10-01)

参考文献数

54

被引用文献数

7

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Vacuolar-type ATPase (V-ATPase) shares its structure and rotational catalysis with F-type ATPase (F-ATPase, ATP synthase). However, unlike subunits of F-ATPase, those of V-ATPase have tissue- and/or organelle-specific isoforms. Structural diversity of V-ATPase generated by different combinations of subunit isoforms enables it to play diverse physiological roles in mammalian cells. Among these various roles, this review focuses on the functions of lysosome-specific V-ATPase in bone resorption by osteoclasts. Lysosomes remain in the cytoplasm in most cell types, but in osteoclasts, secretory lysosomes move toward and fuse with the plasma membrane to secrete lysosomal enzymes, which is essential for bone resorption. Through this process, lysosomal V-ATPase harboring the a3 isoform of the a subunit is relocated to the plasma membrane, where it transports protons from the cytosol to the cell exterior to generate the acidic extracellular conditions required for secreted lysosomal enzymes. In addition to this role as a proton pump, we recently found that the lysosomal a3 subunit of V-ATPase is essential for anterograde trafficking of secretory lysosomes. Specifically, a3 interacts with Rab7, a member of the Rab guanosine 5ʹ-triphosphatase (GTPase) family that regulates organelle trafficking, and recruits it to the lysosomal membrane. These findings revealed the multifunctionality of lysosomal V-ATPase in osteoclasts; V-ATPase is responsible not only for the formation of the acidic environment by transporting protons, but also for intracellular trafficking of secretory lysosomes by recruiting organelle trafficking factors. Herein, we summarize the molecular mechanism underlying secretory lysosome trafficking in osteoclasts, and discuss the possible regulatory role of V-ATPase in organelle trafficking.

著者

Yugo Takagi Shun Nishikado Jumpei Omi Junken Aoki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.8, pp.1008-1021, 2022-08-01 (Released:2022-08-01)

参考文献数

145

被引用文献数

5

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Lysophospholipids are phospholipids with only one fatty acid. During the past two decades, it has become apparent that lysophospholipids are not merely degradation products but have various physiological and pathological functions in vivo via G protein-coupled receptor (GPCR)-type receptors. These include lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), lysophosphatidylinositol/lysophosphatidylglucose (LPI/LPtdGlc), and lysophosphatidylserine (LysoPS). This review focuses on identifying the functions of the receptors, enzymes, transporters, and carrier proteins required for these four lysophospholipids to function as lipid mediators. We also note that many of advances in this field have been made by Japanese pharmaceutical scientists.

著者

Yuki Koshino Hiroaki Tanaka Takakiyo Tatsumichi Yuuri Houchi Jun Nishimura Shinji Kosaka

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.10, pp.1482-1488, 2022-10-01 (Released:2022-10-01)

参考文献数

20

被引用文献数

1

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This study aimed to evaluate the effects on the medical economy of the use of tracing reports by pharmacy-based pharmacists for pharmaceutical interventions, including to reduce leftover medicines. These effects were estimated by analyzing 267 tracing reports issued by pharmacy pharmacists over a period of 1 year, 2020–2021. We estimate that these interventions created cost savings of USD108170.02/year (USD104800 via pharmaceutical interventions, USD3370.02 via interventions to reduce leftover medicines). The cost savings from pharmaceutical interventions prompted by patient follow-up was estimated to be USD47650. The medical economic effect per tracing report was estimated to be USD392.51 from pharmaceutical interventions, USD12.62 from reducing leftover medicines, and USD445.33 from pharmaceutical intervention prompted by patient follow-up. Overall, therefore, pharmaceutical interventions by pharmacy pharmacists using tracing reports, including those designed to reduce leftover medicines, may benefit the medical economy.

著者

Masamitsu Maekawa Keitaro Miyoshi Aya Narita Toshihiro Sato Yu Sato Masaki Kumondai Masafumi Kikuchi Katsumi Higaki Torayuki Okuyama Yoshikatsu Eto Hiroshi Sakamaki Nariyasu Mano

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.9, pp.1259-1268, 2022-09-01 (Released:2022-09-01)

参考文献数

65

被引用文献数

3

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As Niemann–Pick disease type C (NPC) is difficult to diagnose owing to its various clinical symptoms; biomarker tests have been developed. Previously, we revealed urinary sulfated cholesterol metabolites as noninvasive biomarkers for NPC. However, LC/tandem mass spectrometry (LC/MS/MS) requires long separation time and large urine volumes. Recently, a basic mobile phase was reported to increase the MS intensity. Thus, we developed a highly sensitive and rapid LC/MS/MS method for analyzing urinary cholesterol metabolites using a basic mobile phase additive. 3β-Sulfooxy-7β-N-acetylglucosaminyl-5-cholenic acid, its glycine and taurine conjugates, 3β-sulfooxy-7β-hydroxy-5-cholenic acid, and 7-oxo form were measured, with selected reaction monitoring in negative ion mode. Oasis HLB and L-column 3 were used for column-switching LC/MS/MS and urine diluted 10-fold was employed as the sample. After trapping, gradient separation was performed using solutions containing 1% (v/v) ammonium solution. On average, a 16-fold increase in peak areas was observed compared to that obtained at pH 5.5 with the mobile phases. Although the previous method needed 60 min for separation from interference peaks, we succeeded to separate them in 7 min with optimized LC condition. Further, all compounds showed good linearity from 0.3–1000 ng/mL, with satisfactory intra- and inter-day reproducibility. The developed method was applied to the urinalysis of healthy participants and NPC patients. Overall, the concentrations of metabolites correlated with those obtained using the previous method. Therefore, we succeeded to increasing MS intensity and shorten LC running time; and the method is useful for the noninvasive diagnostic screening of patients with NPC.

著者

Takara Ohto Manami Konishi Hiroki Tanaka Koji Onomoto Mitsutoshi Yoneyama Yuta Nakai Kota Tange Hiroki Yoshioka Hidetaka Akita

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.2, pp.299-302, 2019-02-01 (Released:2019-02-01)

参考文献数

14

被引用文献数

12 15

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While the use of in vitro-transcribed mRNA (IVT-mRNA) in therapeutics is a rapidly expanding area, the transfection of the exogenous IVT-mRNA is accompanied by a risk of immune activation. This immunological defense mechanism suppresses cellular translation process and can reduce transfection efficiency to a considerable extent. In the present study, we investigated the in vitro effects of Integrated Stress Response Inhibitor (ISRIB), and dexamethasone, a steroidal anti-inflammatory drug, on the transfection activity of a lipid nanoparticle (LNP) that was composed of ionizable lipids and IVT-mRNA. In the case of transfection to mouse embryonic fibroblast (MEF) cells, ISRIB mainly enhanced the transfection activity at an early stage of transfection (0–6 h). In contrast, dexamethasone caused an increase in transfection activity at intermediate-late stages of transfection (4–48 h). We also investigated the in vivo effects of dexamethasone using an LNP on that the IVT-mRNA and lipid-conjugated dexamethasone (Dex-Pal) were co-loaded. The intravenous administration of the LNP successfully enhanced the protein expression in a mouse liver by up to 6.6-fold. Collectively, the co-delivery of an anti-inflammatory drug is a promising approach for enhancing transfection efficiency of IVT-mRNA.

著者

Toshinori Hirai Hidefumi Kasai Masahiro Takahashi Satomi Uchida Naoko Akai Kazuhiko Hanada Toshimasa Itoh Takuya Iwamoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.7, pp.948-954, 2022-07-01 (Released:2022-07-01)

参考文献数

35

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Some population pharmacokinetic models for amiodarone (AMD) did not incorporate N-desethylamiodarone (DEA) concentration. Glucocorticoids activate CYP3A4 activity, metabolizing AMD. In contrast, CYP3A4 activity may decrease under inflammation conditions. However, direct evidence for the role of glucocorticoid or inflammation on the pharmacokinetics of AMD and DEA is lacking. The pilot study aimed to address this gap using a population pharmacokinetic analysis of AMD and DEA. A retrospective cohort observational study in adult patients who underwent AMD treatment with trough concentration measurement was conducted at Tokyo Women’s Medical University, Medical Center East from June 2015 to March 2019. Both structural models of AMD and DEA applied 1-compartment models, which included significant covariates using a stepwise forward selection and backward elimination method. The eligible 81 patients (C-reactive protein level: 0.26 [interquartile range; 0.09–1.92] mg/dL) had a total of 408 trough concentrations for both AMD and DEA. The median trough concentrations were 0.49 [0.31–0.81] µg/mL for AMD and 0.43 [0.28–0.71] µg/mL for DEA during a median follow-up period of 446 [147–1059] d. Three patients received low-dose oral glucocorticoid. The final model identified that AMD clearance was 7.9 L/h, and the apparent DEA clearance was 10.3 L/h. Co-administered glucocorticoids lowered apparent DEA clearance by 35%. These results indicate that co-administered glucocorticoids may increase DEA concentrations in patients without severe inflammation.

著者

Keita Yaginuma Shuichi Tanabe Takuya Miyano Hiroshi Nakagawa Satoshi Suzuki Shuichi Ando Manabu Kano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.9, pp.855-863, 2020-09-01 (Released:2020-09-01)

参考文献数

24

被引用文献数

3

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In-line monitoring of granule water content during fluid bed granulation is important to control drug product qualities. In this study, a practical scale-free soft sensor to predict water content was proposed to cope with the manufacturing scale changes in drug product development. The proposed method exploits two key ideas to construct a scale-free soft sensor. First, to accommodate the changes in the manufacturing scale, the process parameters (PPs) that are critical to water content at different manufacturing scales were selected as input variables. Second, to construct an accurate statistical model, locally weighted partial least squares regression (LW-PLSR), which can cope with collinearity and nonlinearity, was utilized. The soft sensor was developed using both laboratory (approx. 4 kg) data and pilot (approx. 25 kg) scale data, and the prediction accuracy in the commercial (approx. 100 kg) scale was evaluated based on the assumption that the process was scaled-up from the pilot scale to the commercial scale. The developed soft sensor exhibited a high prediction accuracy, which was equivalent to the commonly used near-infrared (NIR) spectra-based method. The proposed method requires only standard instruments; therefore, it is expected to be a cost-effective alternative to the NIR spectra-based method.

著者

Norifumi Shimizu Chiaki Hara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.8, pp.1279-1282, 2020-08-01 (Released:2020-08-01)

参考文献数

18

被引用文献数

1 3

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Clinical studies, especially those in animal models, have provided evidence that chronic stress may play a role in the etiology of psychiatric diseases, such as depression. Because chronic stress activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the excessive secretion of glucocorticoids, the chronic stimulation of glucocorticoid receptors (GRs) may be involved in the pathogenesis of depression. To further investigate the relationship between GR activation and depression, we used the synthetic glucocorticoid dexamethasone (DEX) and the GR antagonist mifepristone to examine the effects of chronic GR stimulation on the circadian rhythms of locomotor activity and serotonergic neurotransmission in the basolateral amygdala (BLA) of rats. Chronic treatment with DEX reduced locomotor activity during the dark phase, without changing overall activity patterns. Measuring the basal release of serotonin in the BLA, using in vivo microdialysis, confirmed that chronic treatment with DEX induced serotonergic hypofunction in the BLA. The co-administration of DEX with mifepristone effectively suppressed the depressive-like symptoms caused by chronic treatment with DEX. Our results provided further evidence for a relationship between GR and depression and suggest that the pharmacological blockade of GR may increase the effectiveness of conventional pharmacotherapies used to treat depression.

著者

Kazuaki Matsumoto Masaru Samura Sho Tashiro Shino Shishido Reika Saiki Wataru Takemura Kana Misawa Xiaoxi Liu Yuki Enoki Kazuaki Taguchi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.7, pp.824-833, 2022-07-01 (Released:2022-07-01)

参考文献数

69

被引用文献数

6

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The target therapeutic ranges of vancomycin, teicoplanin, and arbekacin have been determined, and therapeutic drug monitoring (TDM) is performed in clinical practice. However, TDM is not obligatory for daptomycin, linezolid, or tedizolid. In this study, we examined whether TDM will be necessary for these 3 drugs in the future. There was no significant difference in therapeutic effects on acute bacterial skin and skin structure infection between linezolid and tedizolid by meta-analysis. Concerning the therapeutic effects on pneumonia, the rate of effectiveness after treatment with tedizolid was significantly lower than with linezolid. With respect to safety, the incidences of gastrointestinal adverse events and blood/lymphatic system disorders related to tedizolid were significantly lower than those related to linezolid. Linezolid exhibits potent therapeutic effects on pneumonia, but the appearance of adverse reactions is indicated as a problem. There was a dose-dependent decrease in the platelet count, and the target trough concentration (Ctrough) was estimated to be 4–6 or 2–7 µg/mL in accordance with the patient’s condition. The efficacy of linezolid may be obtained while minimizing the appearance of adverse reactions by performing TDM. The target therapeutic range of tedizolid cannot be achieved in immunocompromised or severe patients. Therefore, we concluded that TDM was unnecessary, considering step-down therapy with oral drugs, use in non-severe patients, and high-level safety. Concerning daptomycin, high-dose administration is necessary to achieve an area under the curve (AUC) of ≥666 as an index of efficacy. To secure its safety, Ctrough (<20 µg/mL) monitoring is important. Therefore, TDM is necessary.

著者

Eui Dong Son Gyu Ho Choi Hyaekyoung Kim Byoungseok Lee Ih Seoup Chang Jae Sung Hwang

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.8, pp.1395-1399, 2007-08-01 (Released:2007-08-01)

参考文献数

24

被引用文献数

26 37

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Alpha-ketoglutarate is a key intermediate in the Krebs cycle, and a rate-limiting cofactor of prolyl-4-hydroxylase. It also has a potent effect on increasing the proline pool during collagen production, but the details underlying the boosting effect on collagen production by α-ketoglutarate remain as yet unreported. To investigate the effects of α-ketoglutarate on procollagen production and wrinkle formation, we conducted experiments in cultured human dermal fibroblasts and UVB-irradiated hairless mice. Based on ELISA measurements, α-ketoglutarate (10 μM) stimulated procollagen production in fibroblasts by 25.6±4.6% compared to vehicle (dH2O)-treated control cells. Also, we demonstrated that α-ketoglutarate increased activities of prolidase, which is known to play an important role in collagen metabolism, in fibroblasts and N-benzyloxycarbonyl-L-proline (Cbz-Pro), prolidase inhibitor, inhibited procollagen synthesis by α-ketoglutarate in fibroblasts. To determine the effect of topically applied α-ketoglutarate on wrinkle formation, α-ketoglutarate (1%) and vehicle (70% propylene glycol, 30% ethanol) were applied on the dorsal skin of UVB-induced hairless mice for twelve weeks. We found that α-ketoglutarate decreased wrinkle formation upon long-term topical application. These results suggest that α-ketoglutarate diminishes UVB-induced wrinkle formation by increasing collagen production, through a pathway that involves prolidase activation. Therefore, application of α-ketoglutarate may represent an effective anti-wrinkle agent for the cosmetic field.

著者

高谷 芳明 内沢 秀光 松江 一 奥崎 文一 鳴海 文昭 佐々木 甚一 石田 邦夫

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.6, pp.846-849, 1994-06-15 (Released:2008-04-10)

参考文献数

13

被引用文献数

20 26

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Squid ink, which has little commercial use and is usually discarded, was extracted using a Tris-HCl buffer (pH 6.8). The extract was fractionated using DEAE Sephacel ion-exchange chromatography and Sephacryl S-300 gel filtration to give a peptidoglycan fraction which exhibited strong antitumor activity against Meth-A fibrosarcoma in BALB/c mice following intraperitoneal administration. The fraction was composed of 7.8% peptide, 57% polysaccharide and 30% pigment. The polysaccharide component had a unique structure with equimolar ratios of GlcA, GalNAc and Fuc. Since the fraction has no direct cytotoxic effect on Meth-A cells, inhibition of tumor growth may be due to stimulation of host-mediated responses.

著者

Emiko Kurisaki Masao Sato Sigeyuki Asano Hirobumi Gunji Mamoru Mochizuki Hajime Odajima Haruki Wakasa Hiroshi Satoh Chiho Watanabe Kouichi Hiraiwa

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Health Science (ISSN:13449702)

巻号頁・発行日

vol.45, no.6, pp.309-317, 1999-12-31 (Released:2008-04-14)

参考文献数

20

被引用文献数

2 1

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It has been assumed that "smelter disease" is caused by sulfuric dioxide. A typical episode resulting in "smelter disease" occurred in Fukushima, Japan. Twenty-seven workers became ill and eventually three of them died. The concentration of mercury (Hg) was found to be higher in all tissues and blood of the three victims than in those of normal Japanese, although the concentrations of zinc, cadmium, copper and lead in all tissues examined were within the normal range. The clinical course after the incident and autopsy findings clarified the cause of death to be acute Hg fume poisoning. To determine the histological localization of Hg and metallothionein (MT), Hg staining by the photo-emulsion method and immunostaining using anti-MT antibody were carried out. Numerous Hg granules were observed in the epithelia of the proximal tubules of the renal cortex using the photo-emulsion histochemical method. The liver of victims contained a few Hg granules in the hepatic cellular cytoplasm and sinusoid. Immunostaining of the kidney showed a strong positive reaction with anti-MT in the proximal tubules outside the medulla. The presence of Hg-bound MT in the kidneys of the victims was confirmed by gel chromatography. This is the first evidence of Hg-MT in the tissues of humans with acute Hg fume poisoning. Mercury might induce the synthesis of MT in human tissues. In addition, fractionation of the supernatants on gel chromatography revealed that most of the Hg in the kidney and lung of the patient who had the most severe renal and lung damage and who was the first of the three victims to die was distributed in high molecular weight protein fractions (HMW) and a small portion of Hg was bound to MT. These findings suggest that the amount of synthesized MT in tissues was not sufficient for MT to bind to Hg. The amount of Hg absorbed into tissues may be too large for MT to protect tissues, and thereby Hg may be bound to HMW.

著者

Kei Kawada Tomoaki Ishida Kohei Jobu Tsuyoshi Ohta Hitoshi Fukuda Shumpei Morisawa Tetsushi Kawazoe Naohisa Tamura Mitsuhiko Miyamura

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.6, pp.720-723, 2022-06-01 (Released:2022-06-01)

参考文献数

24

被引用文献数

3

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Aggression is the most common adverse effect of antiepileptic drugs (AEDs). This study aimed to investigate the association of aggression with AED use. The reporting odds ratio (ROR) from adverse event reports, submitted to the Japanese Adverse Drug Event Report database between 2004 and 2020, was used to calculate and investigate the association between AEDs and aggression. We also analyzed the association of aggression with the combined use of AEDs and the relationship between AED-associated aggression and patient characteristics. A total of 433 patients developed aggression. Significant aggression signals were detected for perampanel (crude ROR: 325.04, 95% confidence interval (CI): 118.48–752.58, p < 0.01), levetiracetam (crude ROR: 17.14, 95% CI: 10.33–26.90, p < 0.01), lacosamide (crude ROR: 16.90, 95% CI: 2.02–62.51, p < 0.01), lamotrigine (crude ROR: 15.98, 95% CI: 9.99–24.39, p < 0.01), valproate (crude ROR: 6.68, 95% CI: 4.27–10.02, p < 0.01), and carbamazepine (crude ROR: 2.47, 95% CI: 1.17–4.59, p < 0.01). The combined therapy with perampanel and levetiracetam had a significant aggression signal (adjusted ROR: 25.90, 95% CI: 1.14–59.10, p < 0.01). In addition, we found that aggression frequently occurred in patients <60 year (adjusted ROR: 2.88, 95% CI: 1.49–5.56, p < 0.01) treated with levetiracetam. These results may be useful for minimizing the risk of aggression during the treatment of AEDs.

著者

内林 政夫

出版者

The Pharmaceutical Society of Japan

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.125, no.7, pp.583-586, 2005-07-01 (Released:2005-07-01)

参考文献数

5

被引用文献数

3 3

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A certain Chinese herbal book presented to the emperor in 1505 shows a drawing of maize under the caption of Yiyi-ren (Job's Tears). Also, a Chinese poem written around 1368 contains a term yumi, which indicates maize. These new findings offer clear evidence that maize existed in China in the pre-Columbian era, or before 1492. Details of this evidence are discussed here.

著者

Babita Shashni Shinya Ariyasu Reisa Takeda Toshihiro Suzuki Shota Shiina Kazunori Akimoto Takuto Maeda Naoyuki Aikawa Ryo Abe Tomohiro Osaki Norihiko Itoh Shin Aoki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.4, pp.487-503, 2018-04-01 (Released:2018-04-01)

参考文献数

45

被引用文献数

34 65

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Detection of anomalous cells such as cancer cells from normal blood cells has the potential to contribute greatly to cancer diagnosis and therapy. Conventional methods for the detection of cancer cells are usually tedious and cumbersome. Herein, we report on the use of a particle size analyzer for the convenient size-based differentiation of cancer cells from normal cells. Measurements made using a particle size analyzer revealed that size parameters for cancer cells are significantly greater (e.g., inner diameter and width) than the corresponding values for normal cells (white blood cells (WBC), lymphocytes and splenocytes), with no significant difference in shape parameters (e.g., circularity and convexity). The inner diameter of many cancer cell lines is greater than 10 µm, in contrast to normal cells. For the detection of WBC having similar size to that of cancer cells, we developed a PC software “Cancer Cell Finder” that differentiates them from cancer cells based on brightness stationary points on a cell surface. Furthermore, the aforementioned method was validated for cancer cell/clusters detection in spiked mouse blood samples (a B16 melanoma mouse xenograft model) and circulating tumor cell cluster-like particles in the cat and dog (diagnosed with cancer) blood samples. These results provide insights into the possible applicability of the use of a particle size analyzer in conjunction with PC software for the convenient detection of cancer cells in experimental and clinical samples for theranostics.

著者

Takashi Nakada Kiyoshi Sugihara Takahiro Jikoh Yuki Abe Toshinori Agatsuma

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.67, no.3, pp.173-185, 2019-03-01 (Released:2019-03-01)

参考文献数

82

被引用文献数

98 230

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A major limitation of traditional chemotherapy for cancer is dose-limiting toxicity, caused by the exposure of non-tumor cells to cytotoxic agents. Use of molecular targeted drugs, such as specific kinase inhibitors and monoclonal antibodies, is a possible solution to overcome this limitation and has achieved clinical success so far. Use of an antibody–drug conjugate (ADC) is a rational strategy for improving efficacy and reducing systemic adverse events. ADCs use antibodies selectively to deliver a potent cytotoxic agent to tumor cells, thus drastically improving the therapeutic index of chemotherapeutic agents. Lessons learned from clinical failure of early ADCs during the 1980s to 90s have recently led to improvements in ADC technology, and resulted in the approval of four novel ADCs. Nonetheless, further advances in ADC technology are still required to streamline their clinical efficacy and reduce toxicity. [fam-] Trastuzumab deruxtecan (DS-8201a) is a next-generation ADC that satisfies these requirements based on currently available evidence. DS-8201a has several innovative features; a highly potent novel payload with a high drug-to-antibody ratio, good homogeneity, a tumor-selective cleavable linker, stable linker-payload in circulation, and a short systemic half-life cytotoxic agent in vivo; the released cytotoxic payload could exert a bystander effect. With respect to its preclinical profiles, DS-8201a could provide a valuable therapy with a great potential against HER2-expressing cancers in clinical settings. In a phase I trial, DS-8201a showed acceptable safety profiles with potential therapeutic efficacy, with the wide therapeutic index.

著者

Masaya Denda Akira Otaka

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.5, pp.316-323, 2022-05-01 (Released:2022-05-01)

参考文献数

53

被引用文献数

1

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The growing interest in artificial proteins modified by synthetic functional units has fueled the demand for their facile preparation. Native chemical ligation (NCL) enables the chemoselective condensation of peptide thioesters with a cysteine-installed synthetic partner and has enjoyed great success in the production of artificial proteins with up to 100–150 residues. A practical method for converting expressed proteins to the corresponding thioesters should lead to significant progress in the NCL-mediated technology. This account describes our recent contributions to the conversion of naturally occurring peptides to the corresponding thioesters by chemical or chemoenzymatic protocols aiming at their future prevalent use in the preparation of sophisticated protein biologics.

著者

Yu Ishima Toru Maruyama Masaki Otagiri Victor T. G. Chuang Tatsuhiro Ishida

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.5, pp.330-333, 2022-05-01 (Released:2022-05-01)

参考文献数

48

被引用文献数

21

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Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high biocompatibility, and a wide variety of drug binding abilities. Albumin is known to distribute widely in the blood and various interstitial fluids and organs. Different albumin receptors skillfully regulate the distribution characteristics of albumin in the body. Albumin receptors are a group of diverse proteins, such as FcRn, gp60, gp18, megalin, cubilin, SPARC, and CD36. Their tissue distributions in vivo are unique, with different albumin’s recognition sites. Therefore, the distribution of albumin in vivo is ingeniously controlled by these multiple albumin receptors. Reevaluation of these albumin receptors opens up new possibilities for applying albumin as a drug delivery carrier. If the tissue distributions of albumin receptors were known and the albumin recognition site of the receptor was identified, organ-specific active targeting would be possible. In this review, we would like to scrutinize what is currently known and share information to develop next-generation albumin carriers that focus on interactions with albumin receptors.