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HM30181A,a potent P-glycoprotein inhibitor,potentiates the absorption and in vivo antitumor efficacy of paclitaxel in an orthotopic brain tumor model

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Cancer Biology & Medicine 2020年第4期17卷 986-1001页

作者： Wu Zeng Betty Yuen Kwan Law Vincent Kam Wai Wong denise so bik chan Simon Wing Fai Mok Joyce Jia Ying Gao Rebecca Ka Yan Ho Xu Liang Jia Hao Li Ming Tsung Lee Weng Li Yoon Michael P Smolinski Johnson Yiu Nam Lau Christopher Wai Kei Lam Manson Fok State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina At he nex Hong Kong Irmo vative Limited Hong Kong China Faculty of Medici ne Macao Un iversity of Science and TechnologyMacaoChina Athenex Inc. New York 14203USA

Objective:Delivery of chemotherapeutic drugs to the brain has remained a major obstacle in the treatment of glioma,owing to the presence of the blood-brain barrier and the activity of P-gp,which pumps its substrate back into the systemic *** aim of the present study was to develop an intravenous formulation of HM30181 A(HM)to inhibit P-gp in the brain to effectively deliver paclitaxel(PTX)for the treatment of malignant ***:Two formulations of solubilized HM were designed on the basis of different solid dispersion strategies:i)spray-drying[polyvinlypyrrolidone(PVP)-HM]and ii)solvent evaporation[HP-β-cyclodextrin(cyclodextrin)-HM].The P-gp inhibition of these 2 formulations was assessed on the basis of rhodamine 123 uptake in cancer *** and brain pharmacokinetic parameters were also determined,and the antitumor effect of cyclodextrin-HM with PTX was evaluated in an orthotopic glioma xenograft mouse ***:Although both PVP-HM and cyclodextrin-HM formulations showed promising P-gp inhibition activity in vitro,cyclodextrin-HM had a higher maximum tolerated dose in mice than did *** study of cyclodextrin-HM revealed a plasma concentration plateau at 20 mg/kg,and the mice began to lose weight at doses above this ***-HM(10 mg/kg)administered with PTX at 10 mg/kg showed optimal antitumor activity in a mouse model,according to both tumor volume measurement and survival time(P<0.05).Conclusions:In a mouse orthotopic brain tumor model,the intravenous co-administration of cyclodextrin-HM with PTX showed potent antitumor effects and therefore may have potential for glioma therapy in humans.

关键词： HM30181A glioma pharmacokinetics paclitaxel P-glycoprotein

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Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara bik-San Lau Ping-Chung Leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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Tonian–Ediacaran Tectonometamorphic History of the Sa'al Complex,Sinai(Egypt):Implications for the Tectonostratigraphic Framework of the Northern Arabian–Nubian Shield

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Acta Geologica Sinica(English Edition) 2022年第5期96卷 1545-1565页

作者： Mohamed W.ALI-bik Suranjan GHOSH NPRABHAKAR Said HAbd El RAHIM Hilmy EMOUSSA Geological Sciences Department National Research Centre(NRC)DokkiCairo 12622Egypt Department of Earth Sciences Indian Institute of Technology BombayMumbai 400076India

The Sa'al Metamorphic Complex(SMC;southern Sinai)encompasses the oldest arc rocks in the Arabian–Nubian Shield,comprising two non-consanguineous metavolcanic successions(the Agramiya Group and the Post-Ra'ayan Formation)separated by the metasediments of the Ra'ayan *** experienced three distinct deformational events(D_(1)–D_(3))and two low-medium grade regional metamorphic events(M_1–M_(2)).The Agramiya Group and the Ra'ayan Formation experienced all tectonometamorphic events(D_1–D_(3)and M_(1)–M_(2)),whereas the Post-Ra'ayan volcanic rocks were only affected by the D_(3)and M_(2)events.D_(1)is an extensional event and is connected to the late Rodinia break-up(~Tonian;900–870 Ma).The M_(1)metamorphism variably affected the older Agramiya Group,the rhyolitic tuffs experiencing lower to upper greenschist facies conditions and the basic and intermediate volcanic rocks undergoing amphibolite facies *** Ra'ayan Formation metasediments experienced upper greenschist to amphibolite facies *** upper greenschist facies M_(2)affected the youngest Post-Ra'ayan volcanic rocks and other stratigraphic *** compressive D_(2)and D_(3)events were coeval with the accretion of dismembered terranes in the assembly of Gondwana.D_(2)can be linked to the Tonian–Cryogenian arc-arc assembly(~880–760 Ma;in Elat and Sinai),whereas D_(3)and the accompanying M_(2)is constrained to 622–600 Ma(Ediacaran).

关键词： deformation microstructure metamorphism Sa'al Metamorphic Complex Arabian–Nubian Shield

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Effectiveness of acupuncture in postoperative ileus: a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2016年第3期36卷 271-282页

作者： Cheong Kah bik Zhang Jiping Huang Yong School of Traditional Chinese Medicine Southern Medical University School of Traditional Chinese Medicine Southern Medical University

OBJECTIVE: To conduct a systematic review and Meta-analysis of the effectiveness of acupuncture and common acupoint selection for postoperative ileus(POI).METHODS: Randomized controlled trials(RCTs)comparing acupuncture and non-acupuncture treatment were identified from the databases Pub Med, Cochrane, EBSCO(Academic source Premier and MEDLINE), Ovid(including EvidenceBased Medicine Reviews), China National Knowledge Infrastructure, and Wanfang Data. The data from eligible studies were extracted and a Meta-analysis performed using a fixed-effects *** were expressed as relative risk(RR) for dichotomous data, and 95% CI(confidence intervals)were calculated. Each trial was evaluated using the CONsoRT(Consolidated Standards of Reporting Trials) and STRICTA(STandards for Reporting Interventions in Controlled Trials of Acupuncture) guide-lines. The quality of the study was assessed using the Grading of Recommendations, Assessment, Development and Evaluation(GRADE) ***: Of the 69 studies screened, eight RCTs were included for review. Among these, four RCTs(with a total of 123 patients in the intervention groups and 124 patients in the control groups) met the criteria for Meta-analysis. The Meta-analysis results indicated that acupuncture combined with usual care showed a significantly higher total effective rate than the control condition(usual care)(RR1.09, 95% CI 1.01, 1.18; P = 0.02). Zusanli(ST 36) and Shangjuxu(ST 37) were the most common acupoints selected. However, the quality of the studies was generally low, as they did not emphasize the use of ***: The results suggested that acupuncture might be effective in improving POI; however,a definite conclusion could not be drawn because of the low quality of trials. Further large-scale,high-quality randomized clinical trials are needed to validate these findings and to develop a standardized method of treatment. We hope that the present results will lead to improved research, result

关键词：肠梗阻针灸系统随机对照试验 Meta分析 MEDLINE 针刺治疗 Pubmed

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Chinese topical herbal medicine gives additive effect on pharmaceutical agent on fracture healing

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Journal of Traditional Chinese Medicine 2019年第6期39卷 853-860页

作者： Siu Wing Sum Shiu Hoi Ting Shum Wai Ting Ko Chun Hay Lau Clara bik San Hung Leung Kim Leung Ping Chung Institute of Chinese Medicine The Chinese University of Hong KongShatinNew TerritoriesHong Kong China State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongShatinNew TerritoriesHong Kong China Department of Orthopaedics and Traumatology The Chinese University of Hong KongShatinNew TerritoriesHong Kong China

OBJECTIVE:To investigate the efficacy on the combination of oral strontium ranelate(Sr R)with a topical Chinese herbal paste on facilitation of fracture ***:An open fracture was created at the mid-shaft of the right tibia of rat.A herbal pastecalled CDR containing Honghua(Flos Carthami),Chuanxuduan(Radix Dipsaci Asperoidis)and Dahuang(Radix Et Rhizoma Rhei Palmati)was *** rats were treated with either CDR topically on the fracture site,or Sr R orally,or their *** turnover biochemical markers in serum were *** of the fracture was analyzed using micro-CT after 14 and 28 d,followed by histomorphometrical ***:Micro-computed tomography analysis revealed that the combined treatment of CDR with600 mg/g Sr R significantly increased the total callus density,mineralized callus volume fraction,mineralized callus mineral content and mineralized callus density of the callus after 28 d of *** result was consistent with the histomorphometrical analysis on the osteoid *** of biochemical markers showed that the combined treatments reduced the bone resorption that occurs temporarily after ***:This study demonstrated that the combined treatment of oral Sr R and topical CDR is effective to promote fracture healing by their additive effect on promoting bone formation and retarding bone resorption.

关键词： Fracture healing Osteogenesis Bone resorption Medicine,Chinese Traditional Integrative medicine Strontium ranelate

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Seropharmacological Study on Osteogenic Effects of Post-Absorption Ingredients of An Osteoprotective Herbal Formula

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Chinese Journal of Integrative Medicine 2017年第1期23卷 25-32页

作者： SIU Wing-sum KO Chun-hay WONG Hing-lok GAO Si SHUM Wai-ting LAU Clara bik-san HUNG Lung-kim LEUNG Ping-chung Institute of Chinese Medicine Chinese University of Hong KongHong KongChina State Key Laboratory of Phytochemistry and Plant Resources in West China Chinese University of Hong KongHong KongChina Department of Orthopaedics and Traumatology Chinese University of Hong KonqHong KongChina

Objective： To further investigate the in vitro effects of an osteoprotective herbal formula ＂ELP＂（Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psora/eae） using seropharmacological approach. Methods： Rats were fed with ELP or its individual component herbs for 2 days. The serum containing the post-absorbed ingredients of the herbal items were collected for cell culture using UMR106 cell, RAW264.7 cell and mesenchymal stem cell （MSC） isolated from the bone marrow of the rats. The effects of the herbal-containing serum on cell toxicity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay; bromodeoxyuridine assay was conducted to measure the cell proliferation of UMR106 cell and MSC; cell activity was measured using colorimetric method, and mRNA expression of runt-related transcription factor 2 （Runx2）, alkaline phosphatase （ALP） and osteopontin （OPN） of UMR106 and MSC as well as matrix metalloproteinase 9 （MMP-9）, tartrate-resistant acid phosphatase （TRAP） and cathepsin K of RAW264.7 were analyzed using real-time reverse-transcription polymerase chain reaction. Results： ELP and its component serum exhibited no cytotoxic effects on the cells. The ELP-containing serum increased the proliferation of UMR106 cell and MSC by 25.7% and 14.4%, respectively and the alkaline phosphatase activity of MSC was increased by 42.6%. On the contrary, it inhibited the RAW264.7 cell differentiation by 29.2%. ELP serum upregulated the Runx2 expression of UMR and MSC by 1.18 fold and 1.27 fold, respectively. It also upregulated ALP and OPN expression in MSC by 1.69- and 2.12-fold, respectively. On the other hand, ELP serum down-regulated MMP-9 and cathepsin K expression of RAW264.7 cell by 0.46- and 0.36-fold, respectively. Conclusions： The serum of the animals fed with ELP contains active ingredients which are effective in promoting osteogenesis and inhibiting osteoclastogenesis.

关键词： osteoporosis seropharmacology osteogenesis herbal formula

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Inhibitory effect of different Dendrobium species on LPS-induced inflammation in macrophages via suppression of MAPK pathways

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Chinese Journal of Natural Medicines 2018年第7期16卷 481-489页

作者： ZENG Qiang Chun-Hay Ko Wing-Sum Siu LI Kai-Kai Chun-Wai Wong HAN Xiao-Qiang YANG Liu Clara bik-San Lau HU Jiang-Miao Ping-Chung Leung Institute of Chinese Medicine The Chinese University of Hong Kong State Key Laboratory of Phytochemistry and Plant Resources in West China The Chinese University of Hong Kong Shenzhen Research Institute The Chinese University of Hong Kong Kunming Institute of Botany Chinese Academy of Sciences

Dendrobii Caulis(DC), named ‘Shihu' in Chinese, is a precious herb in traditional Chinese medicine. It is widely used to nourish stomach, enhance body fluid production, tonify "Yin" and reduce heat. More than thirty Dendrobium species are used as folk medicine. some compounds from DC exhibit inhibitory effects on macrophage inflammation. In the present study, we compared the anti-inflammatory effects among eight Dendrobium species. The results provided evidences to support Dendrobium as folk medicine, which exerted its medicinal function partially by its inhibitory effects on inflammation. To investigate the anti-inflammatory effect of Dendrobium species, mouse macrophage cell line RAW264.7 was activated by lipopolysaccharide. The nitric oxide(NO) level was measured using Griess reagent while the pro-inflammatory cytokines were tested by ELISA. The protein expressions of inducible NO synthase(iNOS), cyclooxygenase-2(COX-2) and mitogen-activated protein kinases(MAPKs) phosphorylation were evaluated by Western blotting analysis. Among the eight Dendrobium species, both water extracts of D. thyrsiflorum ***(DTW) and D. chrysotoxum Lindl(DCHW) showed most significant inhibitory effects on NO production in a concentration-dependent manner. DTW also significantly reduced TNF-α, MCP-1, and IL-6 production. Further investigations showed that DTW suppressed iNOS and COX-2 expression as well as ERK and JNK phosphorylation, suggesting that the inhibitory effects of DTW on LPS-induced macrophage inflammation was through the suppression of MAPK pathways. In conclusion, D. thyrsiflorum *** was demonstrated to have potential to be used as alternative or adjuvant therapy for inflammation.

关键词： Dendrobium species Anti-inflammation Macrophage MAPK pathways

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Concurrent stenoses: A common etiology of stroke in Asians

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World Journal of Clinical Cases 2014年第6期2卷 201-205页

作者： bik Ling Man Yat Pang Fu Department of Medicine and Geriatrics Tuen Mun Hospital

Atherosclerosis of cerebral vessels is a common cause of stroke. Racial differences in the distribution of cerebrovascular occlusive disease are well *** stenosis is more common in Caucasians,while intracranial stenosis is more common in Asians,Hispanics and African-Americans. Concurrent atherosclerosis of extracranial and intracranial vessels is common in Asians. The incidence of concurrent stenoses ranges from 10% to 48% in patients with symptomatic cerebrovascular disease. The long-term prognosis of these patients is poor and they are at high risk of further vascular events or death. The purpose of this review is to examine the epidemiology, risk factors,stroke mechanism and genetics of concurrent stenoses and to discuss strategies for treatment.

关键词： Atherosclerosis Concurrent stenosis Stroke Asians

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A Commentary: Herbal Medicine Offers Great Potential in Support of Metronomic Cancer Therapy

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Journal of Cancer Therapy 2017年第2期8卷 86-95页

作者： Clara bik-San Lau Chun-Kwok Wong Ping-Chung Leung Partner State Key Laboratory of Phytochemistry and Plant Resources in West China The Chinese University of Hong Kong Hong Kong Institute of Chinese Medicine The Chinese University of Hong Kong Hong Kong Department of Chemical Pathology The Chinese University of Hong Kong Hong Kong Metronomic Global Health Initiative Marseille France

Background: In spite of the advances in Cancer treatment, limitations exist. Refractory cases and late presentations are particularly worrying. The uncertainty of cure and the high costs have led to the popularly of complementary and alternative medicine in cancer treatment. Herbal medicine has particular attraction because it has been shown to be working on a multi-targets direction: promoting apoptosis of cancer cells, anti-angiogenesis and immunomodulating. Research on creating a simple herbal formula with multiple effects of cancer control has started and showed in laboratory platforms promising results. Metronomic Chemotherapy: Attention on the use of old oral cytotoxic drugs in small doses for refractory and late cancer cases has started more than a decade. Satisfactory and good results have been found to be related to anti-angiogenesis, immunomodulations and cancer cell apoptosis. These findings are comparable to the use of multiple targets herbal medicine. Conclusion: Assumption is made that metronomic chemotherapy, combined with herbal medicine could be achieving synergistic effects and would be affordable to all patients.

关键词： Cancer Metronomic Treatment Herbal Medicine

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A Potential Anti-metastatic Chinese Herb Andrographis paniculata—Its In Vitro Activities in Esophageal Cancer Cells and Endothelial Cells

A Potential Anti-metastatic Chinese Herb Andrographis panicu...

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第十四届全国中药和天然药物学术研讨会

作者： Grace Gar-Lee Yue Julia Kin-Ming Lee Kar-Man chan Kwok-Pui Fung Philip Wai-Yan Chiu Clara bik-San Lau The Chinese University of Hong Kong

＜正＞Esophageal cancer is associated with high postoperative recurrence and systemic *** adjuvant chemotherapy and concurrent radiation have shown favourable efficacies,searching for alternative treatments for metast...

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