著者

Mariko Kawana Akime Miyasato Miyui Funato Keigo Nagatani Norifumi Suzuki Chiharu Onoda Hidenori Fujimoto Rintaro Ohno Ayuko Kusakabe Mio Kiribayashi Kazuyo Nakamura Masayoshi Kondo Ayumi Ozeki Kousuke Okamoto Hideya Kokubun

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1444-1450, 2023-10-01 (Released:2023-10-01)

参考文献数

13

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In Japan, a low-dose transdermal fentanyl (TDF; 0.5 mg) has been approved to address pain in opioid-naïve patients with cancer; however, efficacy and safety data are lacking. To determine the efficacy and safety of TDF, patients with opioid-naïve cancer pain prescribed TDF (0.5 mg/d) and oral oxycodone sustained-release formulation (OXY) 10 mg/d were extracted from electronic medical and nursing records. Overall, 40 and 101 subjects were analyzed in the TDF and OXY groups, respectively. Compared with baseline (median [minimum, maximum]) values, changes in the Numerical Rating Scale (NRS) score on days 1, 3, and 7 post-administration were as follows: TDF (0 [−5, 4]) and OXY (−1.0 [−8, 3]); TDF (−1.5 [−6, 3]) and OXY (−2.0 [−8, 4]); and TDF (−2.0[−6, 3]) and OXY (−3.0[−8, 5]), respectively. No significant difference was observed between the groups on days 1 and 3; however, the change in the NRS on day 7 was significantly higher in the OXY group than that in the TDF group. Regarding adverse events, nausea occurred in 12.5 and 13.9% of patients in the TDF and OXY groups, respectively, while 12.5% of TDF- and 10.9% of OXY-treated patients experienced somnolence, revealing similar occurrence in both groups. However, constipation was more common in the OXY group (TDF: 50.0%, OXY: 71.3%). No serious adverse events (e.g., respiratory depression) were observed in either group. Low-dose TDF (0.5 mg), available only in Japan, showed comparable efficacy and safety to OXY (10 mg/d) and can be a first choice for opioid-naïve patients with cancer pain.

著者

Tomoaki Ishida Kei Kawada Kohei Jobu 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.4, pp.460-466, 2022-04-01 (Released:2022-04-01)

参考文献数

34

被引用文献数

2

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Bofutsushosan is a traditional Japanese Kampo medicine. In recent years, it has been reported to be effective in the treatment of lifestyle-related diseases, and its use is increasing. However, side effects from bofutsushosan administration are common, with drug-induced liver injury being the most frequently reported complication. In this study, we analyzed the Japanese Adverse Drug Event Report (JADER) database regarding the occurrence of liver injury after bofutsushosan administration. The results showed that bofutsushosan presented a significant reporting odds ratio (ROR) signal [crude ROR 14, 95% confidence interval (CI) 12–17; p < 0.001], indicating liver injury. Furthermore, the incidents of adverse events following bofutsushosan administration, as recorded in the JADER database, were higher in women aged between 30 and 59 years. The results of logistic regression analysis in patients taking this agent showed that females in the aforementioned age range had higher odds of developing drug-induced liver injury (adjusted ROR 5.5, 95% CI 2.8–11; p < 0.001). Therefore, although bofutsushosan is a useful drug for lifestyle-related diseases, it may be necessary to refrain from its overuse, and caution should be taken during its occasional use to avoid severe adverse events.

著者

Renfeng Qiu Shuxiao Chen Fang Hua Shuai Bian Jianfeng Chen Gang Li Xuejun Wu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.9, pp.1254-1262, 2021-09-01 (Released:2021-09-01)

参考文献数

60

被引用文献数

8

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Betanin, a bioactive ingredient mostly isolated from beetroots, exhibits a protective effect against cardiovascular diseases. However, its effects on abdominal aortic aneurysm (AAA) have not been elucidated. In this study, an AAA model was constructed by infusion of porcine pancreatic elastase in C57BL/6 mice. Mice were then administered with betanin or saline intragastrically once daily for 14 d. Our results showed that treatment with betanin remarkably limited AAA enlargement and mitigated the infiltration of inflammatory cells in the adventitia. The increased expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) was also significantly alleviated following betanin treatment. Furthermore, betanin suppressed the activation of toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) signaling in the aortic wall, and downregulated the levels of tissue-reactive oxygen species as well as circulating 8-isoprostane by stimulating the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Taken together, these data suggest that betanin may attenuate AAA progression and may be used as a therapeutic drug against AAA.

著者

Norihisa Noguchi Hidemasa Nakaminami Keisuke Nakase Masanori Sasatsu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.9, pp.1469-1473, 2011-09-01 (Released:2011-09-01)

参考文献数

25

被引用文献数

16 19

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Probiotics are additives containing live microbes that beneficially affect a host by improving the properties of the host intestinal microflora. Recently, advances in medical treatments have led to increased numbers of immunocompromised patients; some patients contract opportunistic infections of Enterococcus species, which are considered non-pathogenic bacteria. To evaluate the safety of probiotics containing Enterococcus strains, we isolated Enterococcus from six probiotic products and compared the pathogenic genes and antimicrobial susceptibility of the probiotic strains to those of clinical isolates. Our study showed that all Enterococcus strains contained in probiotic products were E. faecium, and no vancomycin-resistant strains were found. In addition, no pathogenic genes, such as ace, agg, gelE, cylM, cylB, cylA, cpd, cob, ccf, efaAfs, efaAfm, espfs, or espfm, were found in the probiotic strains. Pulsed-field gel electrophoresis (PFGE) analysis showed obvious genetic differences between the probiotic strains and the clinical isolates. The data suggested that the probiotic Enterococcus strains were not transmitted to hospitalized patients. Therefore, our results strongly suggest that probiotic products are unlikely agents for causing opportunistic infections.

著者

Yo Shinoda Masahiro Akiyama Takashi Toyama

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.9, pp.1162-1168, 2023-09-01 (Released:2023-09-01)

参考文献数

109

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Methylmercury (MeHg) is the causal substrate of Minamata disease and a major environmental toxicant. MeHg is widely distributed, mainly in the ocean, meaning its bioaccumulation in seafood is a considerable problem for human health. MeHg has been intensively investigated and is known to induce inflammatory responses and neurodegeneration. However, the relationship between MeHg-induced inflammatory responses and neurodegeneration is not understood. In the present review, we first describe recent findings showing an association between inflammatory responses and certain MeHg-unrelated neurological diseases caused by neurodegeneration. In addition, cell-specific MeHg-induced inflammatory responses are summarized for the central nervous system including those of microglia, astrocytes, and neurons. We also describe MeHg-induced inflammatory responses in peripheral cells and tissue, such as macrophages and blood. These findings provide a concept of the relationship between MeHg-induced inflammatory responses and neurodegeneration, as well as direction for future research of MeHg-induced neurotoxicity.

著者

Kunio Kosaka Toshio Yokoi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.11, pp.1620-1622, 2003 (Released:2003-11-01)

参考文献数

13

被引用文献数

49 57

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Nerve growth factor (NGF) is a factor vital for the growth and functional maintenance of nerve tissue. The authors found that a rosemary (Rosmarinus officinalis L.) extract enhanced the production of NGF in T98G human glioblastoma cells. Furthermore, the results indicated that carnosic acid and carnosol, which are major components of the rosemary extract, were able to promote markedly enhanced synthesis of NGF.

著者

Takashi Kitahara Nao Koyama Junichi Matsuda Yuko Aoyama Yoichi Hirakata Shimeru Kamihira Shigeru Kohno Mikiro Nakashima Hitoshi Sasaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.27, no.9, pp.1321-1326, 2004 (Released:2004-09-01)

参考文献数

36

被引用文献数

78 88

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The objective of this study was to investigate the antimicrobial activities of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus (MRSA). The antimicrobial activity of saturated fatty acids and fatty amines was determined by oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96). Lauric acid, the most effective among the saturated fatty acids, showed antimicrobial activity at 400 μg/ml against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA. The minimal inhibitory concentration (MIC) of fatty amines depended on each hydrophobic chain length. The MIC of myristylamine was 1.56 μg/ml; most effective of the fatty amines. In time-kill curves, lauric acid and myristylamine produced a bactericidal effect and a bacteriostatic effect at 4-fold the MIC, respectively. The antimicrobial activities of lauric acid and myristylamine were decreased by human plasma. Cytotoxicity of 3 saturated fatty acids and 3 fatty amines was examined in cultured endothelial cells. Although cytotoxicity of fatty amines was severer than that of saturated fatty acids, myristylamine showed the highest value of apparent therapeutic index among them. DOX-96 was useful for screening antimicrobial substances, especially in the case of insoluble substances. We found that myristylamine showed anti-MRSA activity comparable to that of vancomycin and teicoplanin.

著者

Yasuyuki Sadzuka Chieko Inoue Saho Hirooka Tomomi Sugiyama Keizo Umegaki Takashi Sonobe

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.28, no.9, pp.1702-1706, 2005 (Released:2005-09-01)

参考文献数

42

被引用文献数

19 19

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We previously showed that theanine, is a major amino acid in green tea, enhanced doxorubicin (DOX) induced antitumor activity. Besides, theanine induced the elevation of glutathione (GSH) level attributable to the increase of glutamate in the liver of mice, namely theanine would reduce the adverse reaction of DOX. Consequently, theanine was thought to be effective against the tissue changes with GSH level reduction. On the other hand, it is suggested excessive uptake of alcohol causes a production of free radicals, a decrease of GSH level, and an increase in the amount of lipid peroxide (LPO) in liver, and shifting to an alcoholic liver injury. Then, aiming at the prevention and medical treatment of a hepatic toxicity by the food components with little toxicity, we have studied the effect of theanine (i.p.) on ethanol metabolism and hepatic toxicity using ethanol (p.o.) single-administered mice. On the 1st hour after ethanol administration, the ethanol concentrations in blood of the theanine combined groups decreased compared with the ethanol-alone group. The alcohol dehydrogenase and aldehyde dehydrogenase activities in the liver increased by combined theanine. Since the elevation of cytochrome P450 (CYP) 2E1 activity was controlled in the theanine-combined groups, it was considered that these disorders attributable to CYP2E1 in ethanol long-term uptake might be avoidable by theanine. Although LPO increased in 3 h after by single-administration of ethanol, the increase was controlled by theanine-administration and was improved until the normal level. In conclusion, it was indicated that theanine was effective against alcoholic liver injury.

著者

Tadashi Fujita Atsushi Kawase Toshiro Niwa Norimichi Tomohiro Megumi Masuda Hideaki Matsuda Masahiro Iwaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.5, pp.925-930, 2008-05-01 (Released:2008-05-01)

参考文献数

45

被引用文献数

36 39

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In a previous study we found that 50% ethanol extracts of immature fruits of Citrus unshiu (satsuma mandarin) have anti-allergic effects against the Type I, II and IV allergic reactions. However, many adverse interactions between citrus fruit, especially grapefruit juice, and drugs have been reported due to the inhibition of cytochrome P450 (CYP) activities. The purpose of this study was to examine the competitive inhibitory effects of extracts from immature citrus fruit on CYP activity. Extracts were prepared from 12 citrus species or cultivars, and were tested against three kinds of major CYPs, CYP2C9, CYP2D6 and CYP3A4, in human liver microsomes. We also estimated the amounts of flavonoids (narirutin, hesperidin, naringin and neohesperidin) and furanocoumarins (bergapten, 6′,7′-dihydroxybergamottin and bergamottin) in each extract using HPLC. Citrus paradisi (grapefruit) showed the greatest inhibition of CYP activities, while Citrus unshiu which has an antiallergic effect, showed relatively weak inhibitory effects. Extracts having relatively strong inhibitory effects for CYP3A4 tended to contain higher amounts of naringin, bergamottin and 6′,7′-dihydroxybergamottin. These results, providing comparative information on the inhibitory effects of citrus extracts on CYP isoforms, suggest that citrus extracts containing high levels of narirutin and hesperidin and lower levels of furanocoumarins such as C. unshiu are favorable as antiallergic functional ingredients.

著者

Tadashi Matsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.3, pp.364-378, 2023-03-01 (Released:2023-03-01)

参考文献数

187

被引用文献数

6

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The interleukin 6 (IL-6) family of cytokines is defined by the usage of gp130, a common β-receptor signaling subunit, which promotes a variety of signals. They induce many biological functions on many cell types, including immune and inflammatory cells. They also exhibit hormone-like features, which are involved in homeostatic processes. Signal transducer and activator of transcription 3 (STAT3) is a significant signaling molecule fundamental in regulating IL-6/gp130 and is highly implicated in pathological conditions; therefore, STAT3 activation is tightly regulated through various mechanisms and at multiple levels. There is a large amount of information about STAT3-interacting proteins, which positively or negatively regulate STAT3 activity. This review is focused on IL-6-mediated signal transduction and the introduction of novel STAT3-binding partners. The review will help develop new strategies for clinically controlling the functions of IL-6/STAT3.

著者

Masaki Hirabatake Hiroaki Ikesue Shintaro Yoshino Mayu Morimoto Toshinari Yamasaki Tohru Hashida Mutsushi Kawakita Nobuyuki Muroi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.8, pp.1065-1071, 2023-08-01 (Released:2023-08-01)

参考文献数

25

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Pazopanib is one of recommended treatment for metastatic renal cell carcinoma (RCC). Despite its effectiveness, patients often difficult to continue pazopanib treatment due to adverse events (AEs). We established an ambulatory care pharmacy practice that enables pharmacist–urologist collaboration to manage patients with RCC. This study evaluated the usefulness of this collaborative management. We retrospectively reviewed the medical records of 51 consecutive patients with metastatic RCC receiving pazopanib at the Kobe City Medical Center General Hospital between April 2014 and December 2020. Our collaborative management was implemented in October 2016. The time to pazopanib discontinuation was compared between patients who started pazopanib before (n = 30) and after (n = 21) the implementation of the collaborative management. A multivariate Cox regression analysis was performed to analyze the factors associated with pazopanib discontinuation. In the collaborative management, the oncology pharmacists had a total of 245 face-to-face patient consultations, and provided 286 suggestions [according to supportive care in pazopanib treatment (214 suggestions) were most frequent], and 236 (82.5%) were accepted by urologists. The median time to discontinuation (6.1 months vs. 2.4 months, p = 0.024) was significantly longer in the after group. Multivariate analysis showed that collaborative management (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.26–0.88, p = 0.017), and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 at pazopanib initiation (HR 3.87, 95% CI 1.47–9.13, p = 0.008) were significantly associated with pazopanib discontinuation. These results suggested that, compared to conventional management, collaborative management is effective at prolonging the time to pazopanib discontinuation.

著者

Kota Sakuraba Yukio Kojima Takaaki Terahara Hidekazu Kuma Yoshihiro Tokudome

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b23-00294, (Released:2023-07-31)

参考文献数

24

被引用文献数

1

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Recently, microneedling as a cosmetic product has attracted attention as one way to improve skin barrier function and moisturizing function to reduce wrinkle formation. However, some cases of erythema and edema have been reported as side effects. In order to develop safer microneedle cosmetics, we investigated whether microneedles can improve skin barrier function and moisturizing function even when applied in a non-invasive manner that does not penetrate the stratum corneum. We established the condition of non-penetrating microneedle application on reconstructed human full-thickness skin models and examined the effect on the skin models when microneedles were applied under this condition. Microneedle application increased the gene expression of serine palmitoyltransferase long chain base subunit (SPTLC) 3, filaggrin, and transglutaminase 1. The amount of ceramide produced by SPTLC was also increased by microneedle application. Gene expression of filaggrin-degrading enzymes and the amount of free amino acids, a product of filaggrin degradation, were also increased by microneedling. These results suggest that non-invasive microneedle application can improve skin barrier function and moisturizing function by increasing the amount of ceramide and natural moisturizing factors.

著者

Kenshi Takechi Yurika Yoshioka Hitoshi Kawazoe Mamoru Tanaka Shingo Takatori Miwako Kobayashi Ichiro Matsuoka Hiroaki Yanagawa Yoshito Zamami Masaki Imanishi Keisuke Ishizawa Akihiro Tanaka Hiroaki Araki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.10, pp.1775-1778, 2017-10-01 (Released:2017-10-01)

参考文献数

17

被引用文献数

7 8

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Treatment with antipsychotic drugs has been associated with hyperprolactinemia. The same antipsychotic drugs have also been associated with side effects such as menstruation disorders. The aim of this study was to evaluate the prevalence of hyperprolactinemia and menstruation disorders in women undergoing antipsychotic treatment. We performed a retrospective chart review study of psychiatric patients who underwent laboratory testing for serum prolactin (PRL) level between March 2011 and March 2015 in Ehime University Hospital. Patients presenting with and without menstruation disorders were evaluated to determine if they presented concomitant hyperprolactinemia. Patients with menstrual disorders had a significant increase in serum PRL level with a mean of approximately 90 ng/mL. Those with menstrual disorders presented increased PRL levels by 2-fold that of patients without menstrual disorder. However, there was no significant difference in the equivalent dose of chlorpromazine between these two groups. Additionally, about 70% of patients with menstrual disorders received risperidone treatment. The receiver operating characteristic curve showed that the optimal cutoff point of serum PRL level associated with the development of menstrual disorders was 60 ng/mL. Based on these results, we concluded that patients with menstrual disorders presented increased serum PRL, and that most of them underwent treatment with risperidone.

著者

Takehiro Yamada Shungo Imai Yasuyuki Koshizuka Yuki Tazawa Keisuke Kagami Naoki Tomiyama Ryosuke Sugawara Akira Yamagami Tsuyoshi Shimamura Ken Iseki

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.7, pp.1112-1118, 2018-07-01 (Released:2018-07-01)

参考文献数

31

被引用文献数

15 17

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Therapeutic drug monitoring for voriconazole, an antifungal agent, is essential for maximizing efficacy and preventing toxicity. The aim of this study was to elucidate the optimal maintenance dose of voriconazole in patients with severe liver cirrhosis (Child–Pugh class C) by reviewing the plasma trough concentrations obtained by therapeutic drug monitoring and daily doses of voriconazole. We retrospectively evaluated 6 patients with Child–Pugh class C cirrhosis who received oral voriconazole treatment and were liver transplant recipients or were awaiting liver transplantation. We compared their voriconazole trough concentrations and daily maintenance doses to those of patients who did not have liver cirrhosis (n=56). We found that plasma voriconazole trough concentrations in all patients with Child–Pugh class C were almost within therapeutic range, and the median plasma trough concentration at steady state was not significantly different from that of patients who did not have liver cirrhosis. In addition, the median daily maintenance dose of voriconazole was significantly lower (2.13 mg/kg/d) than that of the control patients (6.27 mg/kg/d), suggesting that trough voriconazole concentrations are elevated in Child–Pugh class C patients. Thus, we conclude that oral voriconazole maintenance doses in patients with Child–Pugh class C should be reduced to approximately one-third that of patients with normal liver function, with the follow-up dose adjusted by therapeutic drug monitoring.

著者

Annisa Rahma Muhammad Miftahul Munir Khairurrijal Anton Prasetyo Veinardi Suendo Heni Rachmawati

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.2, pp.163-173, 2016-02-01 (Released:2016-02-01)

参考文献数

45

被引用文献数

93 117

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An electrospun fiber of polyvinyl(pyrrolidone) (PVP)–Tween 20 (T20) with curcumin as the encapsulated drug has been developed. A study of intermolecular interactions was performed using Raman spectroscopy, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The Raman and FT-IR studies showed that curcumin preferrably interacted with T20 and altered PVP chain packing, as supported by XRD and physical stability data. The hydroxyl stretching band in PVP shifted to a lower wavenumber with higher intenstity in the presence of curcumin and PVP, indicating that hydrogen bond formation is more intense in a curcumin or curcumin–T20 containing fiber. The thermal pattern of the fiber did not indicate phase separation. The conversion of curcumin into an amorphous state was confirmed by XRD analysis. An in vitro release study in phosphate buffer pH 6.8 showed that intermolecular interactions between each material influenced the drug release rate. However, low porosity was found to limit the hydrogen bond-mediated release.

著者

Satoshi Sato Hiroyoshi Ariga Hiroshi Maita

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.7, pp.1010-1014, 2023-07-01 (Released:2023-07-01)

参考文献数

16

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Recently, the finding of recurrent mutations in the spliceosome components in cancer has indicated that the spliceosome is a potential target for cancer therapy. However, the number of small molecules known to affect the cellular spliceosome is currently limited probably because of the lack of a robust cell-based approach to identify small molecules that target the spliceosome. We have previously reported the development of a genetic reporter to detect the cellular levels of small nuclear ribonucleoproteins (snRNPs), which are subunits of the spliceosome, using a split luciferase. However, the original protocol was designed for small scale experiments and was not suitable for compound screening. Here, we found that the use of cell lysis buffer used in blue native polyacrylamide gel electrophoresis (BN-PAGE) dramatically improved the sensitivity and the robustness of the assay. Improved assay conditions were used to discover a small molecule that altered the reporter activity. Our method may be used with other cellular macromolecular complexes and may assist in the discovery of small bioactive molecules.

著者

Masao Nakamura Akira Shiga Ami Iimori Takumi Matsuzaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.7, pp.1004-1009, 2023-07-01 (Released:2023-07-01)

参考文献数

17

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Human lactoferrin (hLF) is a glycosylated globular iron-binding protein with high functional versatility that elicits anticancer, neuroprotective, and anti-inflammatory effects. Some of the diverse functions of hLF are induced after its internalization into various cells via cell surface endocytosis receptors, such as proteoglycans, which contain glycosaminoglycan (GAG) chains. We have previously demonstrated that an hLF derivative comprising the N-terminal half of hLF (referred to as the N-lobe) is internalized by intestinal enterocyte Caco-2 cells. However, the relationship between the intracellular uptake of the N-lobe and its pharmacological activity remains poorly understood. Here, we report that the N-lobe is efficiently internalized by lung cancer cells via endocytic pathways, suppressing their proliferation. Moreover, the N-lobe showed higher intracellular uptake than hLF. We found that the N-lobe was internalized into the human lung cancer cell lines PC-14 and PC-3 via clathrin- and/or caveolae-mediated endocytosis. Intracellular uptake of the N-lobe was inhibited when an equimolar concentration of chondroitin sulfate (CS)-E, a GAG subtype involved in malignant transformation and tumor metastasis, was added. The inhibitory effect of the N-lobe on PC-14 cell proliferation decreased with the addition of CS-E in a dose-dependent manner, suggesting that the CS-recognizing sequence on the N-lobe is necessary for its internalization or that the CS proteoglycan on cancer cells acts as an endocytosis receptor. These results suggest that the efficient endocytic uptake of the N-lobe is important for its antiproliferation effects on lung cancer cell lines. Thus, the N-lobe presents a promising drug candidate for cancer treatment.

著者

Yusuke Tabuchi Masayuki Tsujimoto Kosuke Yamamoto Ryo Shimizu Tadashi Kosaka Koichi Sakaguchi Naoya Dobuchi Kohshi Nishiguchi Keisuke Shikata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.7, pp.964-968, 2023-07-01 (Released:2023-07-01)

参考文献数

16

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Trastuzumab is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) that is indicated for the treatment of HER2-positive breast cancer. The administration of biologics, such as trastuzumab, frequently causes infusion reactions (IRs) with fever and chills. This study aimed to clarify the risk factors for IRs in trastuzumab therapy. Between March 2013 and July 2022, 227 patients with breast cancer who started trastuzumab therapy were included in this study. The severity of IRs was graded according to the Common Terminology Criteria for Adverse Events, Version 5.0. The incidence of IRs in trastuzumab therapy was 27.3% (62/227). Dexamethasone administration was significantly different between the IR and non-IR groups in patients receiving trastuzumab therapy (univariate analysis, p < 0.001; multivariate analysis, p = 0.0002). Without dexamethasone, the severity of IRs in the pertuzumab combination group (Grade 1, 8/65; Grade 2, 23/65) was significantly higher than that in the non-pertuzumab group (Grade 1, 9/37; Grade 2, 3/37; p < 0.05). Our findings suggest that the risk of IRs is significantly higher in patients not premedicated with dexamethasone in trastuzumab therapy and that the concomitant use of pertuzumab without dexamethasone increases the severity of IRs caused by trastuzumab.

著者

Atsuo Fujito Keiichi Hiramoto Masashi Imai Shota Tanaka Kazuya Ooi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b23-00108, (Released:2023-05-17)

参考文献数

30

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Anticancer drugs exhibit many side effects, including skin pigmentation, which often lowers patient quality of life. However, the mechanism of pigmentation caused by anticancer drugs remains unknown. The purpose of this study was to elucidate the mechanism of anticancer drug-induced skin pigmentation using 5-fluorouracil (5-FU), a widely used anticancer drug. Specific pathogen-free, 9-week-old Hos:HRM-2 male mice were intraperitoneally administered 5-FU daily for 8 weeks. Skin pigmentation was observed at the end of the study. Mice treated with 5-FU were also administered inhibitors of cAMP, α-melanocyte-stimulating hormone (α-MSH), and adrenocorticotropic hormone (ACTH) for analysis. Administration of oxidative stress, nuclear factor-kappa B (NF-κB), cAMP, and ACTH inhibitors reduced pigmentation in 5-FU-treated mice. These results indicate that the oxidative stress/NF-κB/ACTH/cAMP/tyrosinase pathway plays an important role in pigmentation in 5-FU-treated mice.

著者

Miko Taniguchi Masakazu Hatano Hiroyuki Kamei Risa Inagaki Shigeki Yamada

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.7, pp.1098-1101, 2019-07-01 (Released:2019-07-01)

参考文献数

11

被引用文献数

2 2

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Long-acting injection (LAI) is a drug administration method that reduces symptoms and prevents recurrence or relapse of schizophrenia. We examined factors related to the continuation of LAI treatment. The study population included patients with schizophrenia who were undergoing LAI treatment involving risperidone, paliperidone, or aripiprazole at Fujita Health University Hospital between October 2009 and June 2017. We assessed the continuation rate of LAI treatment at six months, and collected patient characteristics such as medication history. Furthermore, we classified patients into two clusters according to the reason for introducing LAI based on a previous study (Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, Heres et al.). The study included 82 patients (mean age, 44.9 ± 15.0 years); the continuation rate of LAI after six months was 63.4%. Factors that affected LAI continuation included cluster II [adjusted odds ratio (OR): 5.74, p = 0.017], switching from the same component as LAI (adjusted OR: 7.13, p < 0.001), and diazepam conversion rate (adjusted OR: 0.88, p < 0.001). LAI significantly improved the continuation rate of treatment in the patient group belonging to cluster II. Furthermore, based on other factors and reasons for discontinuation, LAI should be preferably commenced in patients with a more stable condition.