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1.
Journal of Experimental Hematology ; (6): 1967-1971, 2021.
Article in Chinese | WPRIM | ID: wpr-922233

ABSTRACT

Thalidomide and its derivatives have been used in the treatment of myelodysplastic syndrome (MDS) because of their anti-angiogenic and immunomodulatory effects. In recent years, some studies have found that thalidomide and its derivatives not only showed significant efficacy in lower-risk MDS patients with del (5q), but also showed advantages in non-del (5q) MDS patients. In addition, the discovery of its molecular targets and new substrates makes it possible to develop a new generation of immunomodulatory drugs (IMiDs) and to design IMiDs-based proteolysis-targeting chimeras. In this review, the new progress in mechanism and clinical application of thalidomide and its derivatives were summarized briefly, so as to provide a more scientific, reasonable and effective scheme to the treatment of MDS.


Subject(s)
Humans , Immunomodulating Agents , Myelodysplastic Syndromes/drug therapy , Thalidomide/therapeutic use
2.
Journal of Experimental Hematology ; (6): 306-310, 2021.
Article in Chinese | WPRIM | ID: wpr-880073

ABSTRACT

In recent years, it is found that the classical IKKα and IKKβ pathway were closely relates with hematological tumors, except the classical pathogenesis, moreover the classical IKKβ pathway is deeply studied. The studies indicated that the IKKβis activated to phosphorylate the NF-κB through multiple cascades under the effect of extracellular IL-6, TNF-α and other stimulating factors. At the cellular level, the classical IKKβcan promote the tumor cell survival and proliferation, reduce the cell apoptosis, and promote the angiogenesis and cell transfer. Although the classical IKKα plays a role in regulating IKKβ activity, but its role in non-classical pathway is more prominent. This review briefly summarizes the latest advance of researches on the pathogenesis of hematological malignancies in term of IKKα and IKKβpathway, so as to provide the theoretic basis for deeply understanding and studying the pathogenesis of hematologic tumors. At present, blocking the classical IKKα and IKKβ pathway has become a new target for treatment of hematological tumors, moreover, some specific inhibitor for IKKα and IKKβpathway have been developed, for example, LY2409881, BMS 345541 and so on. Most of these drugs are in clinical trials and display some good anti-tumor effects.


Subject(s)
Humans , Cell Survival , Hematologic Neoplasms , I-kappa B Kinase/metabolism , NF-kappa B/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha
3.
Chinese Journal of Pathophysiology ; (12): 566-571, 2018.
Article in Chinese | WPRIM | ID: wpr-701162

ABSTRACT

Glioma,a common primary brain tumor, is considered to be incurable, and easy to relapse.The median survival of the patients with glioma after treatment is only 15 to 19 months.The high heterogeneity of glioma is the main reason leading to poor clinical treatment,and the underlying mechanism is closely related to the cell origin of glioma. Therefore,to elucidate the cell origin of glioma is important to further study the mechanism of tumor formation and develop effective treatment programs.For a long time,studies have attempted to speculate on the cell origin of glioma based on the morphological characteristics,but agreements still haven't been reached.This review focuses on the most probable origin cells,such as neural stem cells,astrocytes,oligodendrocyte progenitor cells and neurons.

4.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 840-844, 2013.
Article in English | WPRIM | ID: wpr-251384

ABSTRACT

Our previous study demonstrated that BM-cyclin 1, a traditional anti-mycoplasma drug, could effectively reverse the multidrug resistance (MDR) of C-A120 cells. The present study aims to explore the reversal effect of BM-cyclin 1 on MDR and its mechanisms in BALB/C nude mice bearing C-A120 cells. Immunoblotting analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to study the change in multidrug resistance-associated protein 2 (MRP2) induced by BM-cyclin 1. We found that the expression levels of MRP2 protein and mRNA in C-A120 cells treated with BM-cyclin 1 were reduced significantly. Chemical colorimetry revealed no significant change in the level of glutathione (GSH). In the xenograft model, the inhibitory rate of C-A120 cells growth in BM-cyclin 1 plus adriamycin (ADM) group was 52%, which was significantly higher than in control group (P<0.01). The immunoblotting and RT-PCR results conclusively demonstrated that BM-cycin 1 could significantly reduce the expression of MRP2 in transplanted tumor. In conclusion, BM-cyclin 1 could effectively reverse the MDR of C-A120 cells in vivo by suppressing the expression of MRP2.


Subject(s)
Animals , Humans , Mice , Antiprotozoal Agents , Pharmacology , Cell Line, Tumor , Diterpenes , Pharmacology , Down-Regulation , Doxorubicin , Pharmacology , Drug Resistance, Multiple , Mice, Nude , Minocycline , Pharmacology , Multidrug Resistance-Associated Proteins , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Xenograft Model Antitumor Assays
5.
National Journal of Andrology ; (12): 387-391, 2013.
Article in Chinese | WPRIM | ID: wpr-350894

ABSTRACT

<p><b>OBJECTIVE</b>To construct a mammalian expression plasmid of the BC022687 gene and investigate the expression and localization of the fusion protein in Chinese hamster ovary (CHO) cells.</p><p><b>METHODS</b>The BC022687 coding sequence was amplified by polymerase chain reaction (PCR) and subcloned into the pEGFP-C1 vector carrying the gene of green fluorescence protein (GFP). After the target region was sequenced, the recombinant plasmid was transfected into CHO cells, and its expression in the CHO cells was determined by Western blot. The localization of GFP-tagged BC022687 in the CHO cells was observed by laser scanning confocal microscopy.</p><p><b>RESULTS</b>BC022687 was successfully cloned into the mammalian expression vector pEGFP-C1, with the restriction fragment length of 950 bp. The expression of the fusion protein was confirmed, with the relative molecular weight of 64 000. The GFP-tagged BC022687 protein was mainly localized in the cytoplasm, and also presented in the centrioles in the transfected CHO cells.</p><p><b>CONCLUSION</b>The successful construction of the plasmid expressing BC022687 in CHO cells has laid a foundation for further studies on the role of this protein in ciliogenesis.</p>


Subject(s)
Animals , Cricetinae , Male , Mice , CHO Cells , Centrosome , Metabolism , Cilia , Metabolism , Cricetulus , DNA, Complementary , Genetic Vectors , Plasmids , Recombinant Fusion Proteins , Genetics , Transfection
6.
Chinese Journal of Industrial Hygiene and Occupational Diseases ; (12): 361-363, 2012.
Article in Chinese | WPRIM | ID: wpr-324261

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the possible effects on nervous system and health condition under the exposure to electromagnetic field.</p><p><b>METHODS</b>Take the resident around the power transmission line as the objects and were divided into 3 groups by the distance from the power transmission line 20 m, 100 m and 500 m, respectively. Some living conditions and health conditions were recorded by face-to-face the questionnaire survey, and Hematological indices of each groups were examined including IgG, IgM, leukocyte formulae, erythrocyte, hemoglobin and platelet.</p><p><b>RESULTS</b>There was no significant difference in each group, according exposure of daily life, such as drinking and smoking (P > 0.05). Compared with the each distance groups, it was presented significant difference between the distance from the power transmission line and the incidence of headache or dizziness, insomnia and easy weary and so on (P < 0.05). In hematology aspect, with the horizontal distance from the power transmission line decreasing, PLT level of residents was reductive and the difference was statistically significant (P < 0.001), whereas leukocyte formulae, erythrocyte, hemoglobin, IgG and IgM had no significant difference among each group (P < 0.05).</p><p><b>CONCLUSION</b>Closely exposure to electromagnetic field may induce headache and so on and decrease the level of PLT.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Cross-Sectional Studies , Electromagnetic Fields , Environmental Exposure , Hematologic Tests , Housing , Nervous System , Power, Psychological , Surveys and Questionnaires
7.
Chinese Journal of Epidemiology ; (12): 683-684, 2008.
Article in Chinese | WPRIM | ID: wpr-313115

ABSTRACT

objective To explore the relationship of migration and oxidative DNA damage by comparative study of oxidative DNA damage effects on people with difierent years of migration among Xinjiang Hasake ethnecity in Shenzhen.Methods Sixty Hasake residents in Shenzhen were selected,and were divided into three groups(n=20)according to the years of migration.Major changes of their life style were investigated.8-hydroxy-2'-deoxyguanosine(8-OH-dG)levels in urine were analyzed,and comet assay of peripheral blood lymphocytes conducted.Results When comparing with the group having a shorter than 1 year of stay,a significant decrease of oliveive tail moment and tail/head length in comet assay in the>3 years group(P<0.05)was observed 8-OH-dG level decreased significantly in 1-3 years group (P<0.05)and>3 years group(P<0.01).Conclusion Our results suggested that life style changes which related to migration might reduce DNA damage in Hasake nationalities.

8.
Chinese Journal of Industrial Hygiene and Occupational Diseases ; (12): 57-60, 2003.
Article in Chinese | WPRIM | ID: wpr-272061

ABSTRACT

<p><b>OBJECTIVE</b>To construct pEGFP-C1-T vector, an eukaryotic expression plasmid of hMTH1 gene antisense RNA.</p><p><b>METHODS</b>The conservative region of hMTH1 gene was amplified by RT-PCR after total RNA being extracted from human embryo lung fibroblast (HLF) and then cloned into pGEM-T vector. After the recombinant plasmid was certified by DNA sequencing, the conservative region of hMTH1 gene was inserted into pEGFP-C1 vector reversedly and pEGFP-C1-T vector was constructed. The efficiency of antisense inhibition was verified by Western blotting after cell transfection.</p><p><b>RESULTS</b>423 bp fragment including conservative region of hMTH1 gene was obtained by RT-PCR. After cloned by pGEM-T vector and certified by DNA sequencing, pEGFP-C1-T vector was successfully constructed by means of recombinant DNA technology. Additionally pEGFP-C1-T vector could efficiently decrease hMTH1 protein level by 46%.</p><p><b>CONCLUSION</b>The efficient expression vector of hMTH1 gene antisense RNA, pEGFP-C1-T has been constructed successfully.</p>


Subject(s)
Humans , DNA Repair Enzymes , Genetic Vectors , Genetics , Phosphoric Monoester Hydrolases , Genetics , Plasmids , RNA, Antisense , Reverse Transcriptase Polymerase Chain Reaction
9.
Chinese Journal of Industrial Hygiene and Occupational Diseases ; (12): 105-107, 2003.
Article in Chinese | WPRIM | ID: wpr-265044

ABSTRACT

<p><b>OBJECTIVE</b>To construct DNA double-strand break (DSB) repair protein hKu70 deficient cell strain and to observe its biological characters for studying the functions of hKu70 gene and the effects of occupational harmfulness factors on DSB repair.</p><p><b>METHODS</b>Human lung fibroblasts (HLF) were transfected with the eukaryotic expression plasmids of hKu70 gene antisense RNA (pEGFP-C1-K) to construct hKu70 protein deficient cells (named as "HLFK"). The protein expression levels of hKu70 gene in HLFC and HLFK were detected by the Western blotting to estimate the effects of antisense inhibition. Morphology, growth character and growth status in soft agar of transfected HLFK were observed.</p><p><b>RESULTS</b>pEGFP-C1-K vector was successfully expressed in HLF. The protein expression level of hKu70 gene in HLFK was decreased by 42% as compared with that in HLFC. No obvious changes of the biologic characters were observed in HLFK.</p><p><b>CONCLUSION</b>The hKu70 protein deficient cell strain was successfully constructed. The hKu70 protein deficiency alone didn't induce obvious changes of the biological characters in HLFK.</p>


Subject(s)
Humans , Antigens, Nuclear , Cell Division , DNA Damage , DNA Helicases , DNA Repair , DNA-Binding Proteins , Ku Autoantigen , RNA, Antisense , Transfection
10.
Chinese Journal of Preventive Medicine ; (12): 183-185, 2003.
Article in Chinese | WPRIM | ID: wpr-257207

ABSTRACT

<p><b>OBJECTIVE</b>To study DNA and nucleus damage in human embryo lung fibroblast (HLF) exposed to hydroquinone (HQ) and its genotoxicity.</p><p><b>METHODS</b>HLF were treated with HQ (0, 10, 20, 40, 80 micro mol/L, respectively) for 3 h and DNA damage was detected by comet assay. HLF was also treated with the same concentrations of HQ for 1 h and micronucleus test was performed after they were cultured for 24 h.</p><p><b>RESULTS</b>Comet assay showed that percentage of cells with tails in each groups treated with varied doses of HQ was 12%, 19%, 42%, 79% and 95%, respectively, with mean tail length of 7.87, 9.35, 11.03, 19.28 and 23.32 micro m, respectively, in an obvious dose-dependent manner (P < 0.05). Very significant increase in percentage of cells with tails and length of their comet tail were observed in those groups treated with HQ of 20, 40 and 80 micro mol/L (P < 0.01). And, proportion of high and severe DNA damage increased with dose of HQ. HQ could also induce formation of micronucleus and abnormal nucleus in all groups treated by varied doses of HQ, with rates of micronucleus and abnormal nucleus of 2%, 3%, 10%, 9% and 15%, and 6%, 7%, 16%, 27% and 28%, respectively, in a significant dose-dependent manner. There was significant increase in rates of micronuclei and abnormal nuclei in cells treated with HQ at doses of 20, 40 and 80 micro mol/L (P < 0.05).</p><p><b>CONCLUSIONS</b>Exposure to HQ could cause DNA and nucleus damage inducing genotoxic effects on HLF.</p>


Subject(s)
Humans , Cell Nucleus , Comet Assay , DNA Damage , Embryo, Mammalian , Fibroblasts , Cell Biology , Hydroquinones , Toxicity , Lung , Cell Biology , Micronucleus Tests
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