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Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry

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World Journal of Gastroenterology 2006年第10期12卷 1536-1544页

作者： Judith YMN Engwegen Helgi H Helgason Annemieke Cats Nathan Harris Johannes MG Bonfrer Jan HM Schellens Jos H Beijnen department of Pharmacy and pharmacology The Netherlands cancer Institute/Slotervaart Hospital AmsterdamThe Netherlands department of Medical Oncology The Netherlands cancer Institute/Antoni van Leeuwenhoek Hospital AmsterdamThe Netherlands department of Gastroenterology and Hepatology The Netherlands cancer Institute/Antoni van Leeuwenhoek Hospital AmsterdamThe Netherlands Ciphergen Biosystems Inc. Freemont CaliforniaUnited States department of Clinical Chemistry The Netherlands cancer Institute/Antoni van Leeuwenhoek Hospital AmsterdamThe Netherlands Utrecht University Faculty of Pharmaceutical Sciences Department of Biomedical analysisUtrechtThe Netherlands

AIM： To detect the new serum biomarkers for colorectal cancer （CRC） by serum protein profiling with surfaceenhanced laser desorption ionisation - time of flight mass spectrometry （SELDI-TOF MS）. METHODS： Two independent serum sample sets were analysed separately with the ProteinChip technology （set A： 40 CRC ＋ 49 healthy controls; set B： 37 CRC ＋ 31 healthy controls）, using chips with a weak cation exchange moiety and buffer pH 5. Discriminative power of differentially expressed proteins was assessed with a classification tree algorithm. Sensitivities and specificities of the generated classification trees were obtained by blindly applying data from set A to the generated trees from set B and vice versa. CRC serum protein profiles were also compared with those from breast, ovarian, prostate, and non-small cell lung cancer. RESULTS： Mass-to-charge ratios （m/z） 3.1×10^3, 3.3× 10^3, 4.5×10^3, 6.6×10^3 and 28×10^3 were used as classitiers in the best-performing classification trees. Tree sensitivities and specificities were between 65% and 90%.Host of these discriminative m/z values were also different in the other tumour types investigated. M/z 3.3× 10^3, main classifier in most trees, was a doubly charged form of the 6.6× 10^3-Da protein. The latter was identified as apolipoprotein C-I. M/z 3.1×10^3 was identified as an N-terminal fragment of albumin, and m/z 28× 10^3 as apolipoprotein A-I. CONCLUSION： SELDI-TOF MS followed by classification tree pattern analysis is a suitable technique for finding new serum markers for CRC. Biomarkers can be identified and reproducibly detected in independent sample sets with high sensitivities and specificities. Although not specific for CRC, these biomarkers have a potential role in disease and treatment monitoring.

关键词： Proteomics Colorectal cancer Biomarker Sensitivity Specificity

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Anti-proliferative and anti-angiogenic activities of ion-channel modulators:In-ovo,in-vitro and in-vivo study

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Asian Pacific Journal of Tropical Biomedicine 2017年第6期7卷 555-562页

作者： Chandana Kamili Ravi Shankar Kakataparthy Uma Maheshwararao Vattikutti Vijay Chidrawar Sindhuri Ammineni department of pharmacology CMR College of Pharmacy department of pharmacology Sri Sai Aditya Institute of Pharmaceutical Sciences and Research department of Pharmacognosy TRR College of Pharmacy department of pharmacology and Toxicology Northern Border University

Objective:Angiogenesis is the development of new blood *** ion channels on endothelium play a vital action in cell proliferation and so in the related *** aimed to investigate the anti-angiogenic effects of Mefloquine(Cl-channel blocker) and4-Aminopyridine(K+ channel blocker).Methods:The anti-angiogenic activities of Mefloquine and 4-Aminopyridine(4-AP)were investigated by in-vivo(sponge implantation method),in-vitro(aortic ring assay)and in-ovo(CAM,Chick Chorioallantoic membrane) *** standard antiangiogenic drug used was ***:In the CAM assay,both the ion channel blockers exhibited noticeable antiangiogenic activity at the concentrations of 10-5M and 10-4M where they significantly exhibited ant proliferative activity by inhibiting the new blood vessel *** the further confirmation anti-angiogenic activity was evaluated in vitro and in *** Rat aortic ring assay reduction in the area of sprouts were observed with 40 m M of 4-AP and7 m M of Mefloquine.A significant reduction in weight of sponges,number of blood vessels formed and hemoglobin content were observed at 4.2 mg/kg of 4-AP and 20 mg/kg and 30 mg/kg of ***:These scientific findings indicate the use of Mefloquine and 4-Aminopyridine in pathological situations involving excessive *** regulation of cell volume,cell migration and proliferation of blood vessels may be the underlying molecular mechanisms.

关键词： Ion-channels Sponge implantation method Aortic ring assay Chick Chorioallantoic membrane

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Targeted cancer therapies

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Chinese Journal of cancer 2011年第1期30卷 1-4页

作者： Li Yan Neal Rosen Carlos Arteaga US Chinese Anti-cancer Association USA department of Medicine and Program in Molecular pharmacology Memorial Sloan-Kettering Cancer Center USA Vanderbilt-Ingram cancer Center Vanderbilt University USA.

With unprecedented understanding of molecular events underlying human cancer in this genomic era, a large number of drugs specifically targeting hypothesized oncogenic drivers to which tumors are potentially addicted to have been developed and continue to be developed. These targeted cancer therapies are being actively tested in clinical trials with mixed successes. This editorial provides an overview on successful targeted cancer drugs on the market and those drugs that are in late clinical development stages. Importantly, the article lays out main challenges in developing molecular targeted therapies and potential path forward to overcome these challenges, as well as opportunities for China in this new era of targeted agents. The editorial serves as an introduction to the Targeted cancer Therapies series that will review in depth of major pathways and drugs targeting these pathways to be published in the coming issues of the Chinese Journal of cancer.

关键词：靶向治疗肿瘤靶向药物分子事件临床试验基因组癌症开发

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Immunogenic cell death effects induced by doxorubicin improved chemo-immunotherapy via restoration of granzyme B activity

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Nano Research 2023年第12期16卷 13250-13258页

作者： Tao Huang Xiaofan Sun Yingqiu Qi Xi Yang Linyao Fan Mengdie Chen Yale Yue Hong Ge Yiye Li Guangjun Nie Huan Min Xianfu Sun department of Breast Disease The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Institute of Advanced TechnologyZhengzhou UniversityZhengzhou 450008China department of pharmacology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450003China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and TechnologyBeijing 100190China

Chemotherapy remains one of the irreplaceable treatments for cancer *** use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously eliciting an antitumor immune response by promoting the recruitment of cytotoxic immune cells and production of granzyme B(GrB).However,numerous malignant cancers adaptively acquired the capacity of secreting serpinb9(Sb9),a physiological inhibitor of GrB,which can reversibly inhibit the biological activity of *** circumvent this dilemma,in this study,an integrated tailor-made nanomedicine composed of tumor-targeting peptide(Arg-Gly-Asp,RGD)decorated liposome,doxorubicin(DOX,an effective ICD inducer),and the compound 3034(an inhibitor of Sb9),is developed(termed as D3RL)for breast cancer *** vitro and in vivo studies show that D3RL can directly kill tumor cells and trigger the host immune response by inducing ***,D3RL can competitively relieve the inhibition of Sb9 to *** restored GrB can not only effectively induce tumor immunotherapy,but also degrade matrix components in the tumor microenvironment,consequently improving the infiltration of immune cells and the penetration of nanomedicines,which in return enhance the combined antitumor *** together,this work develops an integrated therapeutic solution for targeted production and restoration of GrB to achieve a combined chemo-immunotherapy for breast cancer.

关键词： immunogenic cell death granzyme B serpinb9 chemo-immunotherapy nanomedicine

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Protective effects of a polysaccharide from Spirulina platensis on dopaminergic neurons in an MPT-Pinduced Parkinson's disease model in C57BL/6J mice

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Neural Regeneration Research 2015年第2期10卷 308-313页

作者： Fang Zhang Jian Lu Ji-guo Zhang Jun-xia Xie department of pharmacology Medical College of Qingdao University department of Pharmacy Xianyang Central Hospital department of pharmacology Taishan Medical College department of Physiology Medical College of Qingdao University

The present study aimed to determine whether a polysaccharide obtained fromSpirulina platensis shows protective effects on dopaminergic neurons. A Parkinson’s disease model was established through the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyr-idine （MPTP） in C57BL/6J mice. Prior to the MPTP injection, some mice were pretreated with intraperitoneal injections of a polysaccharide derived fromSpirulina platensis once daily for 10 days. The results showed that the immunoreactive staining and mRNA expression of the dopa-mine transporter and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra, were signiifcantly increased in mice pretreated with 800 mg/kg of the poly-saccharide compared with those in MPTP-treated mice. The activities of superoxide dismutase and glutathione peroxidase in the serum and midbrain were also increased signiifcantly in mice injected with MPTP after pretreatment with the polysaccharide fromSpirulina platensis. By con-trast, the activity of monoamine oxidase B in serum and midbrain maintained unchanged. These experimental ifndings indicate that the polysaccharide obtained fromSpirulina platensis plays a protective role against the MPTP-induced loss of dopaminergic neurons in C57BL/6J mice, and that the antioxidative properties of this polysaccharide likely underlie its neuroprotective effect.

关键词： nerve regeneration polysaccharide from Spirulina platensis Parkinson’s disease MPTP dopaminergic neurons antioxidation neural regeneration

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Tumor suppressor p53 and metabolism

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Journal of Molecular Cell Biology 2019年第4期11卷 284-292页

作者： Juan Liu Cen Zhang Wenwei Hu Zhaohui Feng department of Radiation Oncology Rutgers Cancer Institute of New Jersey Rutgers University State University of New Jersey New Brunswick NJ 08903 USA department of pharmacology Rutgers Cancer Institute of New Jersey Rutgers University State University of New Jersey New Brunswick NJ 08903 USA

p53 plays a key role in tumor suppression. The tumor suppressive function of p53 has long been attributed to its ability to induce apoptosis, cell cycle arrest, and senescence in cells. However, recent studies suggest that other functions of p53 also contribute to its role as a tumor suppressor, such as its function in metabolic regulation. p53 regulates various metabolic pathways to maintain the metabolic homeostasis of cells and adapt cells to stress. In addition, recent studies have also shown that gain-offunction (GOF) mutant p53 proteins drive metabolic reprogramming in cancer cells, contributing to cancer progression. Further understanding of p53 and its GOF mutants in metabolism will provide new opportunities for cancer therapy.

关键词： p53 tumor suppressor mutant p53 gain-of-function metabolism

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Erythropoiesis-stimulating agents in the management of cancer patients with anemia: a meta-analysis

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Chinese Journal of cancer Research 2014年第3期26卷 268-276页

作者： Xiaomei Li Zhi Yan Dexiao Kong Wen Zou Jihua Wang Dianshui Sun Yuhua Jiang Chengyun Zheng cancer Center of the Second Hospital Shandong University Institute of Biotherapy for Hematological Malignancies Shandong University Cardiovascular department of the Second Hospital Shandong University Hematology department of the Second Hospital Shandong University pharmacology department of the Second Hospital Shandong University

Background： Erythropoiesis-stimulating agents （ESAs） are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a recta-analysis. Methods： The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials （n=2,387） in cancer patients with 〈11 g/dL hemoglobin （Hb） at the baseline and target Hb （for stopping ESA treatment） at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism （VTE）, hypertension, and on-study mortality. The results are expressed as pooled odds ratio （OR）. Publication bias was assessed using funnel plot analysis. Results： ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval （CI）： 5.85 to 10.53, P〈O.O01] and reduced the red blood cell （RBC） transfusion rate （OR 0.52, 95% CI： 0.42 to 0.65, P〈0.001）. ESAs did not increase the accumulated adverse events （OR 0.95, P=0.82）, or the on-study mortality （OR 1.09, P=0.47）. Conclusions： ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.

关键词： Adverse events anemia cancer erythropoiesis-stimulafing agents (ESAs)

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Is Regular Probiotic Practice Safe for Management of Sepsis?

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Chinese Journal of Integrative Medicine 2022年第2期28卷 185-192页

作者： Rishabh Kumar Alok Shiomurti Tripathi Nidhi Sharma Gaaminepreet Singh Lucy Mohapatra department of pharmacology ISF College of PharmacyMoga(Punjab)India department of pharmacology Amity Institute of PharmacyAmity UniversityLucknow(UP)India

For decades,the gut has been thought to play an important role in sepsis *** is a serious life-threatening,chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit *** have dual roles in polymicrobial sepsis *** may induce sepsis in many cases and may prevent its prognosis in many *** evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor,interleukin-10(IL-10),IL-6,etc.,in *** addition,probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in *** contrary,probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced ***,in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing *** review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.

关键词： sepsis probiotics microbial flora immune system

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Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells

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Chinese Journal of cancer 2014年第2期33卷 115-122页

作者： Zhi-Kun Qiu Dong Shen Yin-Sheng Chen Qun-Ying Yang Cheng-Cheng Guo Bing-Hong Feng Zhong-Ping Chen State Key Laboratory of Oncology in South China department of Neurosurgery/Neuro-oncology Sun Yat-sen University Cancer Center department of pharmacology Guangdong Pharmaceutical University department of Oncology The Affiliated Jiangyin Hospital of Southeast University Medical College

O6-methylguanine DNA methyltransferase(MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells(GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide(TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line(SF-767) and 7 MGMT-negative cell lines(U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB(NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines(P 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132(an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone(P < 0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.

关键词：神经胶质瘤 MGMT 替莫唑胺干细胞耐药性 DNA甲基转移酶 NF-κB 核因子-κB

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Pharmacological effects of ethanol extract of Egyptian Artemisia herba-alba in rats and mice

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Asian Pacific Journal of Tropical Biomedicine 2016年第1期6卷 44-49页

作者： Gehad Abdel Raheem Abdel Jaleel Heba Mohammed Ibrahim Abdallah Nawal E.L.Sayed Gomaa pharmacology department National Research Centre

Objective:To investigate some pharmacological effects including gastroprotective,antiinflammatory,analgesic,antipyretic and in vitro antioxidant effects of Artemisia herbaalba extract in different experimental ***:Inflammation was induced in rat paw by subcutaneous injection of 1%(v/v)carrageenan *** was induced in mice by intraperitoneal injection of 0.6%(v/v) acetic acid *** was induced using Brewer's yeast *** lesion was induced in rats by oral administration of 99% *** anti-inflammatory,analgesic,antipyretic and gastroprotective activities of Artemisia herba-alba extract were investigated *** vitro antioxidant effect was investigated using DPPH free ***:The plant extract showed anti-inflammatory effect in carrageenan-induced paw edema in rats,analgesic effect against acetic acid-induced writhing,and antipyretic activity in Brewer's yeast model of ***,it was shown to be a gastroprotective agent against ethanol-induced gastric *** plant also exhibited a free radical scavenging potential in an in vitro antioxidant study using ***:The results validate the use of the investigated plant in traditional medicine for different ailments.

关键词： Artemisia herba-alba Gastric ulcer Inflammation Antioxidant Rats Mice

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