Studies On Chemical Constituents Of Uroacitides (CDA-II) And Quality Standard Of GLM

With the rapid development of research in biomedicine,cancer experts have constantly been renewing recognition to cancers,scientists have introduced individualized therapies to patients because different molecular expreesion profiles may induce different medicine reactions,the schedule of individualized therapies can enhance the therapeutic effect of cancer therapy.In recent years,cancer experts investigated several fields such as targeting drug,design of administration route using new technology,and drug intelligentification,generated many new strategies,methods and means of cancer therapy.To aim directly at the molecular targets of cancer cells and act upon cell receptors or signaling pathway which can improve cell growth, targeted therapy possesses specific anti-tumor effect.and reduced toxicity.The existing treatments and technologies provide paradigm to cancer patients,initiate the new field of cancer chemotherapy.Abnormal methylation enzymes play a central role in cancer.Uroacitides(CDA-â…¡)is one of preparations derived from fresh human urine,in which includes organic acids,micromolecule polypeptides,and amino acids,etc.As a cell differentiation inducer,CDA-â…¡can impel cancer cell synthesize demethylation DNA by inhibiting methylation enzymes,in order to achieve the purpose of ultimate differentiation.So far the pre-clinical studies indicate that CDA-â…¡can inhibit different kinds of cancer cells proliferation and lead apoptosis.CDA-â…¡is the direct differentiation inducer compared with retinoic acid,interferon,Vitamin D3,methylenediamide,dimethyl sulfoxide and phorbol ester which are indirect differentiation inducer.It exert effects on abnormal methylation enzymes directly.Both direct and indirect differentiation inducers including uroacitides have the common bioactivity to induce the production of oligoisonucleosides in cancer cells.But there are not as much receptors which indirect differentiation inducers can bind with,thereby limiting therapeutic spectrum.While uroacitides is the broad-spectrum differentiation inducer,without confinement of receptors,thus it has a very encouraging prospect.Cancer a kind of dysplasia diseases is delimiting longevity and the quality of human life, especially the carcinoma.People have been seeking safe and effective anticancer drugs for a long time.In human urine there are many natural anticancer substances produced by human's body itself with low toxicity and uroacitides(CDA-â…¡)is one of preparations derived from fresh human urine,in which includes cell differentiation inducer,differentiation helper inducer and anticachexia substances.CDA-â…¡has been approved by the State Drug Administration of China to be marketed(approval number:H20041029)as a class one new drug.As a novel anticancer agent,CDA-â…¡is used for treating patients with malignant tumours in Japan,USA and China. However,so far,there are a large array of problems require solution about investigations. concerned with CDA-â…¡,the main problems include instability of micromolecule polypeptides which are usually affected by temperature,oxidizing agent,metal ion,etc.In additional,because of their weak polarity,it is difficult to obtain the single constituent using conventional separation method,and hard to qualitation and quantitation.To our knowledge,the reliable analysis and activity studies about chemical constituents of CDA-â…¡have so far not been reported in detail,as a result,the quality standard was not established in time.Because of the complicated constituents,instability of CDA-â…¡,it is difficult to isolate and purify the active compounds.In the present paper,we groped the proper test condition to separate and analyze the chemical constituents of CDA-â…¡using advanced instruments,such as preparative liquid chromatograph,LC-MS.The result of preliminary studies shown that CDA-â…¡included over 20 micromolecule polypeptides,some dozens of organic acids, a part of amino acids,etc.There are several satisfactory discoveries,although investigation about these chemical constitutents and bioactivity need to develop.The result can provide scientific proof for the ulterior optimization of preparation formulation,establishment of quality standard, improvement of production technology.This work primarily studied the anti-tumor activity of chemical constitutents,it was hoped to provide scientific proof for further exploitation.In the present paper,we elucidated the status and perspectives of cancer,preparation,anticancer mechanisms and clinical application of CDA-â…¡,isolation,analysis and structure determination of the main chemical constitutents, activity studies in cancer cell line and further destination.Besides the present work,we also studied quality standard of GLM,a polypeptide synthesized by our group.GLM was synthesized using lysine,glutamic acid,alanine and tyrosine,the of GLM has so far not been established in China,we studied it in detail in accordance with relative literatures and government standard, established protocol of the quality standard,gain the satisfactory result,further study of this topic is now underway in our laboratory.