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ABSTRACT: Numerous studies have documented that in cancer therapy flavonoids extracted from traditional Chinese medicine have anti-tumor activity or can enhance efficiency of chemotherapy in combination with chemotherapeutics. Thus, an awareness of flavonoids is needed by physicians and medical researchers. This review provides evidence about anti-hepatocellular carcinoma activity of flavonoids. First, as a common employed in vitro model, profile of HepG2 is shown. Second, the intracellular signaling pathways induced by flavonoids which inhibit the HepG2 cell line are summarized. Third, study situation of anti-HBV/HCV activity of flavonoids is shown. Our review is aimed at providing an understanding of anti-HBV/HCV activity and anti-HCC mechanisms of flavonoids, and an outlook on flavonoids application on cancer therapy.
Drug discoveries & therapeutics. 02/2013; 7(1):1-8.
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ABSTRACT: Intractable and rare diseases are an important public health issue and a challenge to medical care. In recent years, much progress has been made in the United States (US), the European Union (EU), and some parts of Asia including Japan, South Korea, and Taiwan, involving specific legislation to encourage discovery and development of orphan drugs, patients' advocacy organizations to provide vast information on intractable and rare diseases and improve patients' access to healthcare, special research programs to strengthen basic and applied research on intractable and rare diseases, and so on. While China is also actively promoting regulation of intractable and rare diseases, but still lags far behind the US, EU, Japan, and other countries and regions with orphan drug legislation. Based on systematic analysis of the current status and future perspectives for intractable and rare diseases in Asia, we recommend that three important aspects of support from government, patients' advocacy organizations and rare disease registry networks, special research programs and global information exchange platform, should be given great attention in promoting the development of intractable and rare diseases research in Asian countries.
Bioscience trends 04/2012; 6(2):48-51. · 0.97 Impact Factor
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J J Gao,
P P Song,
S Tamura,
K Hasegawa,
Y Sugawara,
N Kokudo,
K Uchida,
R Orii,
F H Qi,
J H Dong, W Tang
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ABSTRACT: Japan-China Joint Medical Workshop (2012) on standardization of perioperative management on hepato-biliary-pancreatic surgery was held by the Center for Medical Standards Research, IRCA-BSSA Group in Japan on April 15-16, 2012. Experts in the fields of surgery, anesthesia, pharmacy, and public health from 21 health institutions from Japan and China presented their research achievements and shared their medical experience of perioperative management on hepato-biliary-pancreatic surgery, which should facilitate building of guidelines for hepatocellular carcinoma and be expected to promote standardized management of liver cancer in Asia.
Drug discoveries & therapeutics. 04/2012; 6(2):108-11.
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Journal of Thrombosis and Haemostasis 02/2012; 10(4):719-22. · 5.73 Impact Factor
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ABSTRACT: Traditional Chinese medicine (TCM) is a typical traditional medicine (TM) with a long-standing history of preventing and curing diseases in China and other countries in East Asia. Standardization of TCM has been a topic of discussion over the past few decades in China with the goal of promoting advances in TCM in China and elsewhere around the world. Many quality and safety control standards for TCMs have been implemented in China, but systematic standards of efficacy have not been established for TCMs until now because of the absence of evidence from clinical practice. Evidence-based medicine (EBM) is the best way to provide evidence from clinical practice, but the quality of current EBM studies of TCM, and especially randomized controlled trials (RCTs) of TCM, needs to be improved. International registration of clinical trials (CTs) of TCM is a good way to provide quality evidence from clinical practice of TCM because it can improve research transparency and ultimately enhance the validity and value of scientific evidence. This evidence will provide the springboard for efforts to standardize TCM.
Drug discoveries & therapeutics. 12/2011; 5(6):261-5.
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ABSTRACT: Magnolol and honokiol, main active compounds from the bark of Magnolia officinalis, have been found to have various pharmacological actions, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties, without appreciable toxicity. Recently, the anti-tumor activity of magnolol and honokiol has been extensively investigated. Magnolol and honokiol were found to possess anti-tumor activity by targeting the apoptosis pathways, which have been considered as targets for cancer therapies. This review will focus on the mechanisms by which magnolol and honokiol act on apoptosis pathways in cancer that have been characterized thus far, including the death receptor mediated pathway, mitochondria-mediated pathway, caspase-mediated common pathway, and regulation of apoptosis-related proteins. These breakthrough findings may have important implications for targeted cancer therapy and modern applications of traditional Chinese medicine.
Drug discoveries & therapeutics. 10/2011; 5(5):202-10.
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ABSTRACT: c-Met, a type of receptor tyrosine kinase, may be significantly associated with the progression of hepatocellular carcinoma (HCC). In addition, des-γ-carboxyprothrombin (DCP) has been found to interact with c-Met and activate HCC cell growth. Therefore, the functional inhibition of c-Met expressed on HCC cells should arrest HCC cell growth. The present study found that the c-Met inhibitor SU11274 suppressed HCC cell growth by inhibiting the activation of c-Met. Furthermore, this inhibitor also neutralized the activation of HCC cell growth resulting from the addition of DCP. These results suggest that the functional inhibition of c-Met might be a target for the development of chemotherapeutic agents for HCC, and especially those that are positive for expression of DCP.
Bioscience trends 04/2011; 5(2):52-6. · 0.97 Impact Factor
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ABSTRACT: Aberrant expressions of KL-6 mucin were proved to be associated with worse tumor behaviors of many carcinomas. This study was to evaluate the expression KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma (CC) and its significance in tumor progression.
KL-6 mucin expressions in 21 patients with CC, 12 with combined hepatocellular and cholangiocarcinoma (cHCC-CC), and 78 with hepatocellular carcinoma (HCC) were detected by immunohistochemical staining. The effects of two glycosylation inhibitors (tunicamycin and benzyl-alpha-N-acetylgalactosamine (BAG)) on CC cell proliferations were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assays. KL-6 mucin expressions were detected by immunocytochemical staining and western blotting after tunicamycin or BAG treatment. Cell adhesive and invasive properties were evaluated by adhesion tests and transwell chamber assays after tunicamycin or BAG treatment.
Positive KL-6 mucin staining was observed in all CC tissues and CC areas of cHCC-CC tissues. Immunocytochemical staining and western blotting showed that KL-6 mucin expressions were significantly reduced after both inhibitors treatment. Cell adhesive properties were significantly decreased after both inhibitors treatment, while cell invasive abilities were significantly decreased after BAG but not tunicamycin treatment.
This study indicated that KL-6 mucin might be a specific tumor target for CC. Therapeutic strategies that target glycosylation of KL-6 mucin may be useful to control aggressive behaviors of CC.
Life sciences 08/2009; 85(9-10):395-400. · 2.56 Impact Factor
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ABSTRACT: KL-6 mucin is a type of MUC1 mucin and its aberrant expression has been shown to be associated with aggressive metastasis and poor clinical outcome in tumors. The present study is to investigate the effects of benzyl-N-acetyl-α-galactosaminide (GalNAc-O-bn), an O-glycosylation inhibitor, on KL-6 mucin expression and invasive properties of a human pancreatic carcinoma cell line, Suit-2 cells. Expression profiles of KL-6 mucin in the cells pretreated with or without 5 mM GalNAc-O-bn for 48 h were examined by Western blotting and immunocytochemical staining and invasive properties were examined by transwell chamber assay. Western blotting and immunocytochemical staining showed that the expression profiles of KL-6 mucin changed significantly after GalNAc-O-bn treatment. Meanwhile, the invasive ability of Suit-2 cells decreased significantly after GalNAc-O-bn treatment (p < 0.05). These results suggest that glycosylation of KL-6 mucin may be closely related to aggressive behaviors of pancreatic cancer cells like metastasis and invasion.
Drug discoveries & therapeutics. 10/2008; 2(5):282-5.
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ABSTRACT: The Japan-China Joint Medical Workshop on Drug Discoveries and Therapeutics 2008 (JCMWDDT 2008) was held from September 29 to October 1, 2008 at The University of Tokyo, Tokyo, Japan. JCMWDDT is an international workshop that is mainly organized by Asian editorial members of Drug Discoveries & Therapeutics ( http://www.ddtjournal.com/home ) for the purpose of promoting research exchanges in the field of drug discovery and therapeutic. This year's JCMWDDT is the second workshop and focused particularly on novel development and technological innovation of anti-influenza agents. The workshop began with an announcement by the Japanese Co-chairperson, Dr. Sekimizu (Department of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan; Editorin- Chief of Drug Discoveries & Therapeutics, DDT) followed by a speech by the Chinese Co-chairperson, Dr. Wenfang Xu (School of Pharmaceutical Sciences, Shandong University, Shandong, China; Editor in China Office of DDT), with additional speeches by Dr. Norio Matsuki (The University of Tokyo, Japan; Editor of DDT) and Dr. Guanhua Du (Chinese Academy of Medical Science, China; Editor of DDT). Fifty-nine titles were presented in 6 specialized sessions (Research Advances in Drug Discoveries and Therapeutics, Drug Synthesis/Clinical Therapeutics, Medicinal Chemistry/Natural Products, Anti-influenza Drugs, Anti-infection/antiviral Drugs, Biochemistry/Molecular Biology /Pharmacology) and a poster session (Drug Discov Ther 2008; 2, Suppl; available at http://www.ddtjournal.com/Announce/index.htm ). An annual outbreak of avian influenza in Asian countries including China and Japan has sparked fears that the virus will mutate and then cause an epidemic in humans. Therefore, Asian researchers need to work together to control this infection. This year's JCMWDDT helped provide an opportunity to reiterate the crucial role of medicinal chemistry in conquering influenza and created an environment for cooperative research in Asian countries. (reported on October 1st, with grateful thanks to all participants) Main program Session I. Research Advances in Drug Discoveries and Therapeutics ● Design, synthesis and preliminary activity assay of influenza virus neuraminidase inhibitors by Wenfang Xu (Shandong University, China) ● Infection disease models with silkworms to evaluate the therapeutic effects of drug candidates by Kazuhisa Sekimizu (The University of Tokyo, Japan) ● Japan's governmental approaches to facilitate drug development process by Makoto Shimoaraiso (Ministry of Foreign Affairs of Japan, Japan) ● Effective detection of the epidermal growth factor receptor mutation by the peptide nucleic acid-locked nucleic acid PCR Clamp by Sakuo Hoshi (The University of Tokyo Hospital, Japan) ● Design and synthesis of p53-MDM2 binding inhibitors by Yongzhou Hu (Zhejiang University, China) Session II. Drug Synthesis/Clinical Therapeutics ● Pharmacogenomics-based clinical studies using a novel fully-automated genotyping system by Setsuo Hasegawa (Sekino Clinical Pharmacology Clinic, Japan) ● Synthesis and biological evaluation of pentacyclic triterpenes as anti-tumor agents by Hongbin Sun (China Pharmaceutical University, China) ● Drug discovery and therapeutics using silkworm as experimental animal by Yasuyuki Ogata (The University of Tokyo, Japan) ● Novel selective estrogen recetpor modulators (SERMs) with unusual structure and biological activities by Haibing Zhou (Wuhan University, China) Session III. Medicinal Chemistry/Natural Products ● Synthesis and properties of isonucleosides incorporated oligonucleotides by Zhenjun Yang (Peking University, China) ● Isolation of antiviral compounds from plant resources using silkworm bioassay by Yutaka Orihara (The University of Tokyo, Japan) ● Synthesis and structural modifcation of tasiamide and the effect of these modifications on in vitro anticancer activity by Yingxia Li (Ocean University of China, China) ● Spirohexalines A and B, novel undecaprenyl pyrophosphate inhibitors produced by Penicillium sp. FKI-3368 by Junji Inokoshi (Kitasato University, Japan) ● Nosokomycins, novel anti-MRSA antibiotics, produced by Streptomyces sp. K04-0144 by OR. Uchida (Kitasato University, Japan) ● In vivo screening for antimicrobial activity of Thai Herbal Medicines using silkworm model by Santad Chanprapaph (Chulalongkorn University, Thailand) ● Novel electrochemical sensor of nitric oxide for screening anti-aging Traditional Chinese Medicine by Zilin Chen (Wuhan University, China) ● Polysacchride from green tea purified by silkworm muscle contraction assay induces innate immunity by increasing the expression of various inflammatory cytokine mRNA in human leukocytes by Saphala Dhital (The University of Tokyo, Japan) Session IV. Anti-influenza Drugs ● Structure-activity relationship of flavonoids as influenza virus neuraminidase inhibitors and their in vitro anti-viral activities by Guanhua Du (Chinese Academy of Medical Sciences and Peking Union Medical College, China) ● Mechanisms and consequences of phagocytosis of influenza virus-infected cells by Yoshinobu Nakanishi (Kanazawa University, Japan) ● Nuclear export inhibitors; a possible target for novel anti-influenza viral drugs by Ken Watanabe (Nagasaki University, Japan) ● Catalytic asymmetric synthesis of oseltamivir phosphate directing toward its stable worldwide supply by Motomu Kanai (The University of Tokyo, Japan) ● Clinical effects of probiotic bifidobacterium in the prevention of influenza virus infections and allergic diseases by Jin-zhong Xiao (Morinaga Milk Industry Co., Ltd., Japan) ● Production of anti-influenza PR8-scFv using a phage display by Normaiza Zamri (Tokai University, Japan) Session V. Anti-infection/Antiviral Drugs ● Emerging infectious diseases and anti-viral drugs: Urgent need to develop effective drugs which cause less resistant virus by Nobuyuki Kobayashi (Nagasaki University, Japan) ● Design, synthesis and antiviral evaluation of novel heterocyclic compounds as HIV-1 NNRTIs by Xinyong Liu (Shandong University, China) ● Antiviral drug screening from microbial products by Eisaku Tsujii (Astellas Pharma Inc., Japan) ● Viral factors that determine the natural course of chronic hepatitis B viral infection by Hiroshi Yotsuyanagi (The University of Tokyo, Japan) ● Effect of andrographolide derivatives having α-glucosidase inhibition, on HBsAg, HBeAg secretion in HepG2 2.2.15 cells by Hongmin Liu (Zhengzhou University, China) ● Current and future antiviral therapy for influenza by Hideki Asanuma (Tokai University, Japan) ● Establishment of an HIV-based pseudotyping system as a safe model for screening inhibitors on bird flu H5N1 entry by Ying Guo (Peking Union Medical Collegee Chinese Academy of Medical Sciences, China) ● Strategy of discovery for novel antibiotics using silkworm infection model by Hiroshi Hamamoto (The University of Tokyo, Japan) ● Potent neuraminidase inhibitors and anti-inflammatory substances from Chaenomeles speciosa by Li Zhang (Chinese Academy of Medical Sciences and Peking Union Medical College, China) ● High-throughput screening assay for hepatitis C virus helicase inhibitors using fluorescence-quenching phenomenon by Hidenori Tani (Waseda University and National Institute of Advanced Industrial Science and Technology, Japan) Session VI. Biochemistry/Molecular Biology/Pharmacology ● A novel conjugate of low-molecular-weight heparin and Cu,Zn-superoxide dismutase: Study on its mechanism in preventing brain reperfusion injury after ischemia in gerbils by Fengshan Wang (Shandong University, China) ● A novel gene fudoh in SCCmec region regulates the colony spreading ability and virulence in Staphylococcus aureus by Chikara Kaito (The University of Tokyo, Japan) ● Water soluble fluorescent boronic acid sensors for tumor cell-surface saccharide by Hao Fang (Shandong Unviersity, China) ● Molecular characterization of the biosynthetic enzyme for the biotechnological production of tetrahydrocannabinol, the active constituent of marijuana by Futoshi Taura (Kyushu University, Japan) ● Galloyl cyclic-imide derivative CH1104I inhibits tumor invasion via suppressing matrix metalloproteinase activity by Xianjun Qu (Shandong University, China) ● Neuroprotection by inhibition of GAPDH-MAO B mediated cell death induced by ethanol by Xiao-Ming Ou (University of Mississippi Medical Center, USA).
Drug discoveries & therapeutics. 10/2008; 2(5):262-3.
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ABSTRACT: N-myc downstream-regulated gene 1 is detected in normal tissue but is down-regulated in cancer tissue. Furthermore, research has suggested that co-expression with p53 is necessary for induction of p53-mediated apoptosis. This study sought to investigate the clinicopathological significance of N-myc downstream-regulated gene 1 and p53 expression in gastric cancer tissue.
Immunohistochemical detection of N-myc downstream-regulated gene 1 and p53 was performed with tissue samples from 96 cases of gastric cancer, and the relationship between expression profiles of proteins and clinicopathological characteristics was statistically analysed.
Positive staining of N-myc downstream-regulated gene 1 was observed in the cytoplasm (22 of 96 cases, 22.9%) and/or nucleus (29 of 96 cases, 30.2%) of cancer cells. In 15 cases (15.6%), both cytoplasm-positive cells and nucleus-positive cells were observed in the cancerous region. The nuclear localization of N-myc downstream-regulated gene 1 was frequently observed in the region of cancerous invasion and was significantly related to lymph node metastasis. In addition, accumulation of p53 protein in the nucleus of cancer cells significantly coincided with the nuclear localization of N-myc downstream-regulated gene 1.
Localization of N-myc downstream-regulated gene 1 and its significant correlation with p53 expression may play an important role in cancer progression.
Digestive and Liver Disease 08/2008; 41(2):96-103. · 3.05 Impact Factor
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R Y Gai,
H L Xu,
X J Qu,
F S Wang,
H X Lou,
J X Han,
M Nakata,
N Kokudo,
Y Sugawara,
C Kuroiwa, W Tang
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ABSTRACT: This article reviewed the process of Traditional Chinese Medicine's modernization on a global scale. This process is motivated by the potential need for traditional medicine as a result of health transitions and increasing drug R&D based on know-how from TCM. The established standards system for modern medicine serves as a basic model yet has limitations in terms of comprehensively evaluating TCM. Spurred by policy committments, research to provide supplements suited to TCM's features and principles is underway. Advanced and interdisciplinary technology and methodology is expected to play an essential role in TCM development.
Drug discoveries & therapeutics. 02/2008; 2(1):2-4.
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ABSTRACT: China's Good Manufacturing Practice (GMP) standards that mainly parallel WHO standards were made compulsory in 2004. However, GMP implementation had both positive as well as negative impacts on the pharmaceutical industry, with negatives including pharmaceutical companies suffering economic hardships, poor execution of GMP standards, and sequent health scares. This report briefly describes the problems with GMP implementation in China.
Drug discoveries & therapeutics. 08/2007; 1(1):12-3.
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ABSTRACT: To investigate the relationship between sialylation of glycoconjugates and clinicopathological characteristics of gastric cancer.
Sialylation of glycoconjugates was examined histochemically in 71 gastric cancers using Maackia amurensis leukoagglutinin (MAL), a lectin that recognizes the trisaccharide sequence NeuAc alpha 2,3Gal beta 1,4GlcNAc/Glc. Positive staining with MAL was observed in the tumour region of all of the samples, but the populations of MAL-positive tumour cells in the tumour region varied among the samples. In the corresponding non-cancerous regions, however, no positive staining was observed. Calculating the percentage of MAL-positive tumour cells as part of the total tumour cells with respect to the MAL-staining index (MI) allowed the gastric cancer to be classified into two distinct groups: high and low levels of MI, with a cut-off level of 40% of MI. Furthermore, statistical analyses using the MI level and clinicopathological characteristics of the tumour indicated that a high MI level in gastric tumour tissues is related to a poorer prognosis.
The appearance of MAL-positive glycoconjugates in gastric tumour cells is associated with the behaviour of gastric cancer.
Histopathology 04/2003; 42(3):239-45. · 3.08 Impact Factor
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ABSTRACT: Background: Des-γ-carboxy prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells in the absence of vitamin K. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. Hence, we aimed to examine the efficacy of vitamin K2 on the production of DCP as well as tumor cell growth and invasion. Methods: Cell growth and viability were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The in vivo efficacy of vitamin K2 was examined in nude mice bearing HCC cells. A 24-well transwell chamber was used to evaluate the motility and invasive ability of HCC cells. Levels of DCP in supernatant of cultures and in serum of mice were measured using an electrochemiluminescence immunoassay method. Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC. Results: Vitamin K2 (2–40 μM) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG2 cells and in serum of nude mice bearing HCC xenografts. The inhibition of DCP was also observed using the assays of Western blot analysis in HCC cultures and immunohistochemical analysis in HCC xenografts in mice. As a result of administration of vitamin K2, the capacity of HCC growth was inhibited and the invasion and migration of tumor cells were decreased. Furthermore, the inhibitory effects of HCC growth were also observed in vivo and the sensitivitywas well correlated with the decrease of DCP in the serum of mice. Conclusion: Vitamin K2 might suppress the growth and invasion of HCC cells via decrease of DCP.
Chemotherapy 08/1970; 55(1):28-35. · 1.82 Impact Factor
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ABSTRACT: AimsAberrant expressions of KL-6 mucin were proved to be associated with worse tumor behaviors of many carcinomas. This study was to evaluate the expression KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma (CC) and its significance in tumor progression.Main methodsKL-6 mucin expressions in 21 patients with CC, 12 with combined hepatocellular and cholangiocarcinoma (cHCC-CC), and 78 with hepatocellular carcinoma (HCC) were detected by immunohistochemical staining. The effects of two glycosylation inhibitors (tunicamycin and benzyl-alpha-N-acetylgalactosamine (BAG)) on CC cell proliferations were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assays. KL-6 mucin expressions were detected by immunocytochemical staining and western blotting after tunicamycin or BAG treatment. Cell adhesive and invasive properties were evaluated by adhesion tests and transwell chamber assays after tunicamycin or BAG treatment.Key findingsPositive KL-6 mucin staining was observed in all CC tissues and CC areas of cHCC-CC tissues. Immunocytochemical staining and western blotting showed that KL-6 mucin expressions were significantly reduced after both inhibitors treatment. Cell adhesive properties were significantly decreased after both inhibitors treatment, while cell invasive abilities were significantly decreased after BAG but not tunicamycin treatment.SignificanceThis study indicated that KL-6 mucin might be a specific tumor target for CC. Therapeutic strategies that target glycosylation of KL-6 mucin may be useful to control aggressive behaviors of CC.
Life Sciences.
