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Objective:To investigate the expression of PRMT5 protein in colorectal cancer tissues and its relationship with recurrence after curative resection.Methods:The clinical data of 154 patients with colorectal cancer who underwent radical resection in Zigong Fourth People′s Hospital from February 2016 to April 2018 were retrospectively reviewed, the colorectal cancer tissues and adjacent tissues samples of them were retained at the time of surgery. The PRMT5 protein expressions in each specimen were determined by immunohistochemistry. The recurrence status of patients during the 3-year postoperative follow-up period was counted, and they were divided into recurrence group and no recurrence group.The positive expression rates of PRMT5 protein in colorectal cancer tissues between the two group was compared, and Cox regression model analysis was used to analyze the influencing factors of recurrence after radical resection of colorectal cancer.Results:The positive expression rate of PRMT5 protein in the colorectal cancer tissues was higher than that in the adjacent tissues: 70.13%(108/154) vs. 16.23%(25/154), there was statistical difference ( χ2 = 91.16, P<0.01). Within 3 years after surgery, the recurrence rate was 20.13%(31/154), and the positive expression rate of PRMT5 protein in the recurrence group was higher than that in the no recurrence group: 93.55%(29/31) vs. 64.23%(79/123), there was statistical difference ( χ2 = 10.16, P<0.05). The results of Cox regression model analysis showed that the tumor stage, lymph node metastasis and positive expression of PRMT5 protein in colorectal cancer tissues were independent risk factors for recurrence after radical resection of colorectal cancer ( P<0.05). Conclusions:The PRMT5 protein shows high expression in colorectal cancer tissues, and it is closely related to postoperative recurrence, and its positive expression can increase the risk of postoperative recurrence in patients with colorectal cancer.
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Scientifically elucidating the mode of action of Chinese medicine has become an urgent challenge to Chinese medicine researchers.Opinions on the mode of Chinese medicine effect are active.The scientific hypothesis that additive effect is the key mode of action for Chinese medicine,trigger the scholars and experts in pharmacology field of Chinese medicine to think and contend.The opinion of additive effect provides a new interpretation for mode of action and action characteristics of Chinese medicine.It plays a positive role in the development of pharmacology of Chinese medicine.According to current research results of traditional Chinese medicine (TCM) and clinical cases,this paper made further thinking and summary on the key mode of action for Chinese medicine.The summary is as follows.The diversity of Chinese medicine structure and complexity of Chinese medicine targets determine the complicated mode of action of Chinese medicine.Mode of action for Chinese medicine is complex and variable,which is to adapt to changes in the environment.The genetic diversity of the body receptors due to evolution and the diversity of Chinese medicine and biological complex network control system have determined that a single component of Chinese medicine is more likely to act synergistically by targeting on different targets.From the point of view of Monarch,Minister,Assistant and Guide theory of Chinese medicine,additive effect has limitation.Therefore,just using additive effect is unable to fully explain the Chinese medicine compatible regularity of Monarch,Minister,Assistant and Guide theory.Additive effect is one of action types for Chinese medicine.It is worth to consider if there has any other more important action type for Chinese medicine.
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The elaboration of the mechanism and pharmacodynamic substance are the main obstacles to the modernization of Chinese medicine.The rich ingredient of Chinese medicine is almost attention,with a research strategy of forward pharmacology.This strategy often neglects the study of trace components of Chinese medicine.Synthetic lethality,a extremely complex gene interactions,is to magnify the effects of the co-regulation of biological effects (＞ 1 000 times).The theory of synthetic lethality has achieved good results in the development of anti-tumor drugs,including the discovery of PARP inhibitors,the clinical use of chemotherapy drug addition and attenuation combination.In view of this,this research model may be used to elucidate trace effective substance.Based on the reverse thinking of "targetcomponent-effect"and clear synergistic targets,the mechanism of traces and weak-potency substance of traditional Chinese medicine was studied,and the synergistic combination of potential was found.
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The interferons(IFNs) are a family of the multifunctional cytokines, which are a kind of highly active and multifunctional glycoproteins.Studies in recent years have shown that IFNs exert a powerful antitumor effect by regulating the proliferation of tumor cells, suppressing tumor metastasis and angiogenesis, and activating antitumor immune response.Combined with other tumor treatment methods, it can inhibit the development of a variety of blood system tumors and solid tumors.In addition, the use of IFNs inducers or IFNs combined with emerging immunotherapy can significantly increase the effectiveness of tumor therapy.This review focuses on our understanding of antitumor mechanism and clinical application of IFNs, and provides some guidance for future research and clinical treatment.
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Tumor metastasis is one of the important biological characteristics of malignant tumor,which is closely related with the prognosis of the cancer patients.High expression of ADAM8 in varieties of tumors was revealed in many recent studies,and such aberrant expression played a crucial role in regulating of tumor metastasis.Studies showed that overexpression of ADAM8 attenuated the intercellular adhesion effect,promoted tumor angiogenesis,and enhanced the degradation of ECM as well as the releasing of cytokines.Therefore,suppression of ADAM8 may lead to inhibition of tumor metastasis,which makes ADAM8 a particular attractive target as it can be used as a prognostic indicator and a potential therapeutic target of malignant tumor.A review about the relations between ADAM8 protein′s abnormal expression and tumor occurrence was discussed in this paper,also include discussion about the mechanisms of ADAM8 protein′s disorder-induced tumor formation,as well as therapeutic strategies based on ADAM8-targeted,which may provide references for follow-up research and clinical treatment.
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Multi-component Chinese medicine has been considered an important developmental direction for traditional Chinese medicine (TCM) formula.Nowadays,it is unfit to target a molecule for preventing or curing a disease because it resulted from multiple of factors and resulted in many indications.Thus,the idea focusing on the multiple targets for therapy is increasingly accepted by physicians and scientists.Here,we conceived a new simplified method for screening the active multi-component Chinese medicine based on the complexity of Chinese medicine,the multi-target property of protein signal transduction and the principle of Chinese medicine prescription.Combined with the traditional knowledge on tumor and latest antitumor research results of Chinese medicine and its compounds,the method was concretely illustrated.It helps us to transform the herbal compounds to new complex drugs targeting multiple signaling.
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The study on tumor metabolism has been gradually be-come a hot spot in recent years .A lot of proteins involved in the regulation of tumor metabolism especially the glucose transporter protein 1(GLUT1).As a key regulatory factor mediating energy metabolism within tumor cells , GLUT1 can regulate the glucose intake and maintain the basic level of metabolism in tumor cells . More importantly, the abnormal expression of GLUT1 was asso-ciated with many kinds of tumors , of which GLUT1 was used to meet the energy requirement for the fast growth of tumor .Thus GLUT1 also played a crucial role in growth , differentiation and metastasis of tumor cells and prognosis of tumors .Meanwhile , as three-dimensional crystal structure of GLUT 1 was determined , it is possible to design the small molecular inhibitors of GLUT 1, which can realize “starve to death” tumor cells.GLUT1 can be a particularly attractive target for tumor treatment and interfer-ence.The relationship between abnormal expression of GLUT 1 protein and tumor metabolism was reviewed . Moreover , the mechanism of tumor metabolism regulated by GLUT 1 protein ex-pression and treatment of cancers were discussed , which may provide references for future research and clinical treatment .
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Aim To discuss the impact of important ac-tive ingredient of garlic diallyl sulfide———DATS on platelet activating factor (PAF ) mediated melanoma metastasis and its mechanisms.Methods ①MTT was used to test the effect of different concentrations of DATS on B16F10 and A375 melanoma cell growth number;②Scratch test and transwell were employed to test the effect of different concentrations of DATS on B16F10 and A375 melanoma cell migration;③ West-ern blot was used to test the effect of DATS on expres-sion of MMP-2,ERK,p38 induced by PFA;④Intrave-nous injection of tumor metastasis model was used to check the inhibition of DATS in PAF-mediated melano-ma metastasis.Results B16F10 cells relative growth rate fell to 73.21% and 48.78%,respectively,when DATS concentration reached 50 and 100 μmol·L-1 . DATS inhibited the levels of PAF-induced migration of melanoma cells B16F10 and vertical migration signifi-cantly,and inhibited B16F10 cells migration induced by PAF through inhibiting the expression of MMP-2, paxillin protein,FAK and other proteins.Conclusion DATS can significantly inhibit PAF-induced tumor metastasis, which is related to the inactivation of MAPKs.
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Tumor metastasis is one of the most important biologi-cal characteristics of malignant tumor, and it is also the main factor resulting in poor prognosis and leading to failure of treat-ment. In recent years, studies have shown that the extracellular matrix ( ECM) of tumor microenvironment plays a critical role in tumor metastasis. Tumor ECM fibrogenesis could form the cross-linked network structure, which not only provides nutrition and support to tumor, also it is necessary to tumor growth and inva-sion. These research results indicate that blocking ECM fibro-genesis may exert an inhibitory effect on tumor metastasis. Therefore, targeting ECM fibrogenesis has become a particularly attractive strategy as it can be used in the treatment of metasta-sis-related diseases. The ECM fibrogenesis in tumor is reviewed in this paper as well as the treatment strategies on tumor metas-tasis by targeting ECM fibrogenesis, which may provide refer-ences for follow-up research and clinical treatment.
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Tumor metastasis is one of the most important biologi-cal characteristics of malignant tumor, and it is also the main factors that cause treatment failure and poor prognosis. Clinical studies have shown that the number of platelets in patients with malignant tumor increased more significantly than that in benign tumor patients and healthy people, which indicate that platelet might be involved in the development process of tumor. Further study found that in the process of cancer spreading to blood, platelet could interact with tumor cells to form tumor emboli, helped tumor cells escape from immune surveillance, thus pro-moted the tumor metastasis. In recent years, related mechanisms on platelets in promoting tumor metastasis were revealed gradual-ly, and several targeted therapies based on platelets were also carried out. This paper reviews the role of platelet in mediating tumor metastasis by hematogenous spread and its mechanisms and discusses the therapy strategies that target platelet, which may provide references for follow-up research and clinical treat-ment.
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Aim To screen the potential inhibitors of post-transcriptional activity of pro-inflammatory media-tor TNF-α from the lipophilic constituents in Chinese Medicine Salvia miltiorrhiza Bunge ( Danshen) , we es-tablished dual luciferase reporter gene system pGL3-TNF-α3′UTR ( 3′untranslated region ) co-transfected with Renilla control gene. Methods Complementary DNA ( cDNA) template was obtained from human um-bilical vein endothelial cells ( HUVECs ) . The full length DNA of TNF-α 3′-UTR was amplified through PCR, and then connected the luciferase reporter vector pGL3-control after enzyme digestion. pGL3-TNF-α 3′UTR constructs were co-transfected with pSVRenilla into the mononuclear macrophages RAW264. 7 cells. The relative activity of reporter genes was measured by dual luciferase reporter ( DLR ) assay system after the stimulus of lipopolysaccharide ( LPS ) in presence or absence of tanshinones compounds. Results The pGL3-TNF-α3′UTR luciferase reporter gene was suc-cessfully constructed. The cloning DNA fragment and sequence were both consistent with the GENBANK da-tabase. LPS significantly induced the relative reporter activityof RAW264 . 7 cells transfected with pGL3-TNF-α 3′UTR. Among four tanshinones compounds, we found only cryptotanshinone could significantly de-crease LPS-induced relative reporter activity. Conclu-sion The pGL3-TNF-α 3′UTR construct combined with DLR assay system was successfully established, which can be used to discover the agents such as cryp-totanshinone that regulate the post-transcription of TNF-α in treatment of inflammatory and malignant dis-eases.
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MTH1 (MutT Homolog1 )as MutT homologous en-zyme,is a nucleotide pyrophosphatase,mainly involved in DNA damage repair process,especially plays an important role in the process of DNA replication in tumor cells.Recent studies have found that MTH1’s function is responsible for the development of a variety of tumors.Studies have shown that,MTH1 can remove tumor cells’oxidative DNA elements detrimental to the function-al structure,protecting tumor cell division and proliferation, maintaining tumor cell survival,however,normal cells do not need MTH1.Therefore,MTH1 may be only closely associated with abnormal cell growth.This makes MTH1 as therapeutic tar-gets that have been paid much attention.This article reviewed the relationship of MTH1 and tumor,discussed the mechanisms of MTH1 in tumor growth MTH1 and tumor treatment,so as to provide reference for clinical research and treatment of tumor.
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AngiotensinⅡ( AngⅡ) is the main functional bioac-tive peptide of the renin angiotensin system,and its basic function is to regulate salt-water homeostasis and blood pressure. Howev-er,recent studies have shown that AngⅡ plays a very important role in tumor formation and angiogenesis by acting on its type 1 receptor (AT1R) as a kind of potential growth factor. This arti-cle is a brief overview of the research on effects of AngⅡ-AT1R system in the process of tumor angiogenesis in recent years.
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<p><b>OBJECTIVE</b>To study the molecular mechanism of anti-tumor effect of Danshensu (DSS) focusing on whether it is related to its antioxidation effect on redox state of non-small cell lung cancer A549 cells and relevant nuclear transcription factors and signal pathway.</p><p><b>METHOD</b>DPPH radical scavenging, ferric reducing, ferrous iron chelating assay and DCFH-DA fluorescence staining of ROS were introduced to detect antioxidant activity and ROS scavenging activity in vitro; MTf was adopted to analyze the effect of DSS on A549 cells viability at different time and dose. Western blot was used to detect the effect of DSS on the protein expression of hypoxiainducible factor HIF-1alpha and redox regulating transcription factor Nrf2 in A549 cells and the phosphorylation of upstream Akt, ERK1/2 MAPK.</p><p><b>RESULT</b>DSS could reduce the ROS level in A549 cells in a dose-dependent manner, which was related to it's strong DPPH radical scavenging activity. Moreover, DSS inhibited A549 cells proliferation in both dose- and time- dependent manner. Further study on molecular mechanism indicated that DSS suppressed redox regulator Nrf2, and down-regulated the phosphorylation of Akt and ERK1/2. However, DSS had no effect on HIF-la expression.</p><p><b>CONCLUSION</b>DSS might have the effect on treating non-small cell lung cancer by scavenging ROS and then inhibiting phosphorylation of Akt, ERK1/2 and down-regulating Nrf2 expression in A549 cells.</p>
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Metabolism , Cell Line, Tumor , Cell Proliferation , Drugs, Chinese Herbal , Pharmacology , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , NF-E2-Related Factor 2 , Metabolism , Oxidation-Reduction , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Reactive Oxygen Species , Metabolism , Transcription Factors , MetabolismABSTRACT
Objective To study the antidepression action of curcumin and to explore its mechanism. Methods Mouse reserpine-induced depression model and mouse tetrabenazine-induced acquired despair model were used to observe the effect of curcumin on relieving depression. According to the hypothesis of monoamine, the effect of curcumin on activating monoamine, and inhibiting reuptake of monoamine neurotransmitters and monoamine oxidase inhibitor (MAOI) were observed. Results Curcumin in the dose of 50 mg/kg and more can relieve melancholic symptoms in mice induced by reserpine and tetrabenazine. Curcumin had no direct activation on monoamine either had no obvious inhibition on reuptake of monoamine neurotransmitters of noradrenalin, 5-hydroxytriptamine and dopamine . However, Curcumin had an obvious effect on improving rat forelimb spasm induced by tryptamine hydrochloride. Conclusion Curcumin acts like a kind of monoamine oxidase inhibitor, which exerts antidepression action by inhibiting monoamine oxidase activity and increasing the concentration of monoamine neurotransmitter in brain.
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Objective To develop a method to determine trace Pb and Cd in mineral water, tap water and sea water. Methods Pb and Cd in the samples were enriched in the sulphydryl cotton column under the conditions that the pH of the samples was adjusted to 7 and collected by washing the column with 4 ml of 0.2 mol/L HCl solution. The concentration of Pb and Cd was determined by flame atomic absorption spectrophotometry. Results Pb and Cd were not detected in four kinds of mineral water samples, but in tap water and sea water, Pb was 1.56 ?g/L and 0.43 ?g/L, Cd was 0.62 ?g/L and 0.07 ?g/L respectively. The rates of recovery were 96.6%-104.0% and RSD was
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AIM To observed the effect of procyanidins on DNA damage induced by carcinogen or hydroxyl radical (OH?),and inhibitory effect on topoisomerase. METHODS Using labeled TdR uptake assay and single cell gel electrophonesis. Topoisomerase was extracted from B16F10 cell lines, used agarose gel electrophoresis assay. RESULTS It was showed that hydroxyl radical (OH?) or different doses of MNNG can induce severe DNA damage of L 929 cell lines. Procyanidins can alleviate the damage induced by MNNG or OH?. It shows certain dose dependent effect relationship . But there is no significant inhibitory against Topo Ⅱ activity by procyanidins even at a dose of 50 ?mol?L -1 . CONCLUSION Procyanidins from grapes seeds can protect DNA damage,but not inhibit topoisomerase activity. This is one of cancer chemoprevention mechanism of Procyanidins.