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Table of Content

    08 October 2020, Volume 47 Issue 10 Previous Issue    Next Issue
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    Original Articles
    miR-1254 inhibits the proliferation and invasion of glioma cells by targeting CSF-1
    Chen Liang, Qin Jun, Lei Junrong, Liu Jun, Wang Lu
    2020, 47 (10):  577-584.  doi: 10.3760/cma.j.cn371439-20200416-00082
    Abstract ( 546 )   HTML ( 428 )   PDF (2472KB) ( 356 )   Save

    Objective To investigate the expressions of miR-1254 and its target gene colony-stimulating factor-1 (CSF-1) in glioma tissues and glioma cells, and the effects of miR-1254 and CSF-1 on the proliferation and invasion of glioma cells. Methods The clinicopathological specimens and paracancerous tissues of 30 patients with glioma who underwent surgical treatment in Shiyan Taihe Hospital of Hubei Province from April 2017 to May 2019 were collected. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect the expression levels of miR-1254 and CSF-1 mRNA in glioma tissues, paracancerous tissues, U87 cells and human brain normal glial cells HEB. The glioma U87 cells were divided into blank control group, mimic NC group, miR-1254 mimic group, and siRNA NC group, CSF-1 siRNA group. The expression levels of miR-1254 and CSF-1 mRNA were detected by qRT-PCR. The protein expression levels of CSF-1 in each group were detected by Western blotting. Dual luciferase reporter gene assay was used to verify the targeting relationship between miR-1254 and CSF-1 gene. CCK-8 method and Transwell invasion experiment were used to detect the proliferation and invasion ability of cells. Results The relative expression of miR-1254 mRNA in glioma tissues was 0.44±0.16, that in adjacent tissues was 1.15±0.28, and there was a statistically significant difference (t=12.914, P<0.001). The relative expression of CSF-1 mRNA in glioma tissues was 1.96±0.27, that in adjacent tissues was 0.98±0.22, and there was a statistically significant difference (t=14.970, P<0.001). The relative expression of miR-1254 mRNA in glioma cells U87 was 0.39±0.11, that in human brain normal glial cells HEB was 1.03±0.02, and there was a statistically significant difference (t=10.113, P=0.008). The relative expression of CSF-1 mRNA in glioma cell U87 was 1.02±0.03, that in human brain normal glial cell HEB was 0.32±0.13, and there was a statistically significant difference (t=9.037, P=0.009). The expression levels of CSF-1 mRNA and protein decreased with the increase of miR-1254 after transfection of miR-1254. The results of dual luciferase reporter gene assay showed that compared with the mimic NC group (1.04±0.12), the fluorescence activity of CSF-1-WT cells in the miR-1254 mimic group (0.31±0.02) was significantly reduced (t=10.430, P<0.001). The difference in cell proliferation ability among the blank control group (0.71±0.01), mimic NC group (0.68±0.04) and miR-1254 mimic group (0.35±0.01) was statistically significant 48 h after transfection (F=252.651, P<0.001). The difference was statistically significant between miR-1254 mimic group and blank control group (P<0.001), and the difference was also statistically significant between miR-1254 mimic group and mimic NC group(P<0.001). The difference in cell proliferation ability among the blank control group (0.71±0.01), siRNA NC group (0.68±0.04) and CSF-1 siRNA group (0.25±0.01) was statistically significant (F=320.309, P<0.001). The difference was statistically significant between CSF-1 siRNA group and blank control group (P<0.001), and the difference was also statistically significant between CSF-1 siRNA group and siRNA NC group (P<0.001). Invasion experiments showed that the difference of transmembrane cells number among the blank control group (365±27), mimic NC group (388±24) and miR-1254 mimic group (83±15) was statistically significant (F=173.915, P<0.001). The blank control group (365±27), siRNA NC group (404±32) and CSF-1 siRNA group (87±14) had statistically significant difference in the number of transmembrane cells (F=141.294, P<0.001). Conclusion The expressions of miR-1254 in glioma tissues and glioma cells U87 are significantly decreased, and the expressions of CSF-1 in glioma tissues and glioma cells U87 are significantly increased. Overexpression of miR-1254 may inhibit the proliferation and invasion of glioma U87 cells by reducing the expression of CSF-1 targetedly.

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    Exosomal miR-196a derived from liver cancer stem cell enhances liver cancer cells resistance to doxorubicin
    Song Quan, Ding Ningling, Xu Ying, Cao Kaiyue, Zhou Sufang, Zhao Aiqin, Pan Yunzhi, Ma Sai
    2020, 47 (10):  585-592.  doi: 10.3760/cma.j.cn371439-20200611-00083
    Abstract ( 527 )   HTML ( 208 )   PDF (1994KB) ( 311 )   Save

    Objective To screen the differentially expressed exosomal miRNAs derived from liver cancer stem cells (LCSCs) and its effect on the malignant biological characteristics of liver cancer cells. Methods miRNA expression profile chip was used to analyze the differentially expressed exosomal miRNA derived from LCSCs. The effects of miRNA on malignant phenotypes of LCSCs were identified. The cells were further treated with doxorubicin at different concentrations (0, 150, 300 μmol/L), and the expression level of miR-196a was detected by quantitative real-time PCR (qRT-PCR). The apoptosis of liver cancer cells cultured by exosomes derived from LCSCs (Exo-NC group) and exosomes derived from miR-196a inhibited LCSCs (Exo-Inhibitor group) and the activity of caspase3/7 under the action of exosomes from LCSCs were detected. Nude mice were randomly divided into Do-PBS group, Do-Exo-Inhibitor group and Do-Exo-NC group using random number table method, with 5 mice in each group, and the effect of miR-196a on nude mice xenograft tumor model with liver cancer cells was analyzed. Results In this study, exosomes were isolated and purified from CD133+ Huh7 stem cell culture supernatant. miR-7162-3p, miR-1910-5, miR-3613-3p, miR-196a and miR-155-5p were up-regulated, while miR-1246 and miR-3613-5p were down-regulated. miR-7162-3p, miR-196a and miR-155-5p in exosomes had important effects on the self-renewal ability of LCSCs. miR-1910-5p, miR-196a and miR-155-5p had important effects on the invasion ability of liver cancer stem cells, among which miR-196a had the most significant inhibitory effect. Treatment for 24 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin was 0.96±0.05, 1.23±0.05 and 2.33±0.03 respectively, with a statistically significant difference (F=996.90, P<0.001). Treatment for 48 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin were 1.02±0.07, 2.35±0.05 and 2.89±0.55 respectively, with a statistically significant difference (F=303.00, P<0.001). When the concentration of doxorubicin was 0 and 300 μmol/L, the apoptosis rates of the Exo-NC group were 9.37%±0.19% and 11.64%±0.27%, and those of the Exo-Inhibitor group were were 18.80%±1.91% and 22.79%±1.57%, with statistically significant differences (t=4.41, P=0.048; t=4.96, P=0.038). When doxorubicin was not used, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.94±0.08 and 0.97±0.09, and those in the Exo-Inhibitor group were 1.56±0.01 and 1.58±0.01, with statistically significant differences (t=11.41, P=0.008; t=6.07, P=0.026). Under 300 μmol/L doxorubicin, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.95±0.07 and 1.36±0.08, and those in the Exo-Inhibitor group were 2.84±0.08 and 3.20±0.14, with statistically significant differences (t=24.20, P=0.002; t=15.78, P=0.004). The results of xenograft tumor in nude mice showed that the tumor volumes of Do-PBS, Do-Exo-Inhibitor and Do-Exo-NC groups increased successively, which were (1 051.86±89.90) mm3, (1 310.91±86.66) mm3 and (2 185.14± 352.34) mm3 respectively, with a statistically significant difference (F=30.28, P<0.001). The weights of the transplanted tumors in the 3 groups increased successively, which were (0.36±0.10) g, (0.39±0.12) g and (0.76±0.16) g respectively, with a statistically significant difference (F=11.81, P=0.002). The expression of miR-196a in tumors was significantly decreased after miR-196a inhibitor transfection. The expression levels of the 3 groups were 1.05±0.16, 0.38±0.08 and 2.17±0.26, with a statistically significant difference (F=48.93, P<0.001). Conclusion The exosomal secreted by LCSCs can enhance the resistance of liver cancer cells to doxorubicin by miR-196a.

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    Research on prediction of pathological complete response after neoadjuvant therapy for rectal cancer based on MRI high-resolution T2WI images
    Lu Haidi, Shen Fu, Lu Jianping, Hao Liqiang
    2020, 47 (10):  593-597.  doi: 10.3760/cma.j.cn371439-20200527-00084
    Abstract ( 663 )   HTML ( 51 )   PDF (1044KB) ( 359 )   Save

    Objective To explore the value of MRI high-resolution T2WI based-radiomics in predicting pathologic complete response (pCR) after neoadjuvant therapy for rectal cancer. Methods This retrospective study included 80 patients with rectal cancer confirmed by postoperative pathology, who underwent high-resolution imaging of rectal MRI before neoadjuvant therapy from January 2018 to March 2019 in our hospital. After manually delineating the volume of interest (VOI) of the lesion in the high-resolution T2WI image, the radiomics features were extracted, and the least absolute shrinkage and selection operator (LASSO) algorithm was adopted to reduce the dimension and select the features that were valuable for tumor pCR. Using Random algorithm, the data were randomly divided into training set (n=64) and test set (n=16) for machine learning, and 4 kinds of machine learning models including decision tree (DT), logistic regression (LR), random forests (RF) and extreme gradient boosting (XGBoost) were established and ROC curves were drawn. The area under the curve (AUC), sensitivity, specificity and 95%CI were respectively calculated, and the difference of ROC curves was compared with DeLong test. Results Among 80 patients with rectal cancer, there were 15 cases by pCR, accounting for 18.75%, and 65 cases were non-pCR, accounting for 81.25%. A total of 1 409 imaging features were extracted. After dimension reduction by LASSO algorithm, 8 most valuable features were selected. The AUC of DT, LR, RF and XGBoost in the test set group was 0.870, 0.801, 0.912, 0.945, the AUC of XGBoost was the largest, and the differences between XGBoost and DT, LR, RF were statistically significant (P=0.008; P=0.006; P=0.009), and the pairwise comparisons of DT, LR, RF showed no statistically significant difference (PLR-RF=0.083; PDT-LR=0.113; PDT-RF=0.879). The sensitivity was 78.57%, 64.29%, 78.57%, 85.71%, and the specificity was 95.38%, 84.62%, 92.31%, 98.46% respectively. The 95%CI was 0.775-0.935, 0.696-0.882, 0.827-0.964, 0.870-0.984. Conclusion The radiomics based on high-resolution T2WI images has predictive value for pCR after neoadjuvant treatment of rectal cancer. XGBoost model has better predictive efficiency than DT, LR and RF, and can be used to guide clinical individualized treatment and related interventions.

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    Analysis of SKA1 gene expression in clear cell renal cell carcinoma and its clinical significance based on bioinformatics database
    Han Jing, Yuan Shuai, Pu Yan, Liu Huibin
    2020, 47 (10):  598-605.  doi: 10.3760/cma.j.cn371439-20200113-00085
    Abstract ( 627 )   HTML ( 38 )   PDF (1882KB) ( 339 )   Save

    Objective To investigate the expression of spindle and kinetochore-associated complex subunit 1 (SKA1) gene in clear cell renal cell carcinoma (ccRCC) and its clinical significance. Methods The venous blood samples of 76 preoperative patients with ccRCC and 24 healthy subjects were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January 2018 to December 2018. The level of SKA1 in whole blood was detected by real-time fluorescence quantitative PCR, and the relationship between SKA1 level and clinicopathological characteristics was analyzed. SKA1 data were retrieved from Oncomine (v4.5), The Human Protein Atlas (THPA) gene databases, The Cancer Genome Atlas (TCGA) databasec (cBioportal) and Gene Expression Omnibus (GEO). The Kaplan-Meier method was used to perform patients' survival analysis based on cBioportal ccRCC data, and the survival rates were compared by log-rank method. The relationship between SKA1 expression level and clinicopathological characteristics was analyzed by χ2 test. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of SKA1 mRNA in ccRCC, and enrichment analysis of SKA1 gene was carried out using KOBAS 3.0 online tool. Results Two studies on the expression level of SKA1 mRNA in ccRCC were retrieved from Oncomine (v4.5) database, and there were 38 samples. The results showed that SKA1 mRNA was highly expressed in ccRCC tissues. Further detection showed that the expression level of SKA1 mRNA in ccRCC tissues was significantly higher than that in normal renal tissues [-2.21(-3.56,-1.59) vs. -3.41(-4.55,-1.65)], and there was a statistically significant difference (Z=2.282, P=0.022). The analysis of THPA online website showed that SKA1 protein showed obvious moderate staining in ccRCC tissues, while weakly positive or no expression in normal renal tissues. SKA1 was mainly located in the plasma membrane, which was consistent with the results of mRNA analysis. The results of cBioportal showed that the expression level of SKA1 was significantly correlated with AJCC staging (χ2=21.352, P<0.001), T staging (χ2=19.967, P<0.001), N staging (χ2=11.323, P=0.003) and M staging (χ2=27.248, P<0.001). The relative level of SKA1 in peripheral blood of 76 patients with ccRCC was 0.301±0.147, and 0.162±0.052 in healthy subjects, with a statistically significant difference (t=7.360, P<0.001). The level of SKA1 was correlated with AJCC staging (t=2.445, P=0.017) and lymph node metastasis (t=2.242, P=0.028). The results were consistent with tissue analysis in cBioportal database. Survival analysis showed that in cBioportal database, the expression level of SKA1 mRNA was related to the overall survival rate and disease free survival rate of patients with ccRCC (χ2=22.440, P<0.001; χ2=23.830, P<0.001). In GEO database, the expression level of SKA1 mRNA was not related to the overall survival rate of patients with ccRCC (χ2=0.241, P=0.632). The results of ROC analysis in cBioportal database showed that when the cut-off value was -0.944, the sensitivity and specificity of SKA1 mRNA in the diagnosis of ccRCC were 100% and 98.7%. The area under the ROC curve (AUC) was 0.991 (95%CI: 0.972-1.000). The results of ROC analysis of 76 patients with ccRCC showed that when the cut-off value was 0.235, the sensitivity and specificity of peripheral blood SKA1 in the diagnosis of ccRCC were 75.0% and 95.8%, and the AUC was 0.837 (95%CI: 0.761-0.914). KOBAS enrichment analysis showed that SKA1 high expression samples were enriched in gene sets such as chromosomal centromeres, microtubule polymerization and depolymerization regulation and mitotic spindle check-up points. Conclusion SKA1 is highly expressed in ccRCC tissues, which is obviously related to the prognosis of patients. It can be used as a diagnostic indicator and potential therapeutic target for ccRCC.

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    Efficacy of olaparib combined with bevacizumab in the treatment of patients with recurrent platinum-sensitive ovarian cancer and its effect on serum HE4, CA125 and CTC levels
    Quan Ruiquan, Zhang Li, Kuang Li, Li Hongbo, Xiao Meixian
    2020, 47 (10):  606-610.  doi: 10.3760/cma.j.cn371439-20191116-00086
    Abstract ( 738 )   HTML ( 37 )   PDF (797KB) ( 384 )   Save

    Objective To observe the efficacy and safety of olaparib combined with bevacizumab in patients with recurrent platinum-sensitive ovarian cancer, and the effect on serum levels of human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125) and circulating tumor cells (CTCs). Methods A total of 96 patients with recurrent platinum-sensitive ovarian cancer admitted to Dongfeng Hospital Affiliated to Hubei Medical College from June 2018 to June 2019 were selected and divided into control group (n=48) and study group (n=48) according to the random number table method. The control group was given doxorubicin liposomes combined with carboplatin chemotherapy for 6 cycles, and the study group was given olaparib combined with bevacizumab, continuous olaparib, and bevacizumab for 6 cycles. The median progression-free survival (PFS), the objective effective rate (ORR), disease control rate (DCR) of the two groups were evaluated, the changes of serum HE4, CA125 and CTCs levels of the two groups after treatment were compared, and the adverse drug reactions of patients during treatment were observed. Results The median PFS of the study group was 8.3 months, which was longer than 5.5 months of the control group, with a statistically significant difference (χ 2=5.134, P=0.025). The ORR and DCR of the study group were 52.08% (25/48) and 81.25% (39/48), which were significantly higher than 31.25% (15/48) and 62.50% (30/48) of the control group, with statistically significant differences (χ2=4.286, P=0.038; χ2=4.174, P=0.041). After 6 cycles treatment, serum HE4 [(123.60±31.52) pmol/L vs. (178.01±46.22) pmol/L], CA125 [(33.52±10.61)U/L vs. (50.32±11.09) U/L] and CTCs [(2.19±0.24) pcs/5 ml vs. (3.25±0.31) pcs/5 ml] of the study group were significantly lower than those of the control group, with statistically significant differences (t=8.489, P=0.025; t=7.562, P=0.032; t=9.341, P=0.017). The incidences of gastrointestinal reactions [35.42% (17/48) vs. 64.58% (31/48)], bone marrow suppression [18.75% (9/48) vs. 41.67% (20/48)], liver and kidney function damage [2.08% (1/48) vs. 14.58% (7/48)], cardiotoxicity [4.17% (2/48) vs. 18.75% (9/48)], allergy reaction [0 (0) vs. 8.33% (4/48)], neurotoxicity [2.08% (1/48) vs. 16.67% (8/48)] and other adverse reactions of the study group were significantly lower than those of the control group, with statistically significant differences (χ2=8.167, P=0.004; χ2=7.584, P=0.006; χ2=4.909, P=0.027; χ2=5.031, P=0.025; χ2=4.174, P=0.041; χ2=6.008, P=0.014). Conclusion For patients with recurrent platinum-sensitive ovarian cancer, olalapril combined with bevacizumab has better curative effect than doxorubicin liposome combined with carboplatin chemotherapy, and can prolong the survival period of patients, down-regulate serum HE4, CA125 and CTCs levels, with low incidence of adverse reactions.

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    Reviews
    Role of FAM3 gene family in tumor
    Liao Chengcheng, An Jiaxing, Tan Zhangxue, Wang Qian, Liu Jianguo
    2020, 47 (10):  611-614.  doi: 10.3760/cma.j.cn371439-20200311-00087
    Abstract ( 793 )   HTML ( 65 )   PDF (658KB) ( 372 )   Save

    Family with sequence similarity 3 (FAM3) gene family is closely related to human tumors, and plays an important role in glucose and lipid metabolism and angiogenesis, and it is related to the occurrence and development of esophageal squamous cell carcinoma, gastric cancer, colon cancer, pancreatic cancer, oral squamous cell carcinoma and breast cancer. Analysis of the role of the FAM3 gene family in glycolipid metabolism and tumors may be of great significance for understanding the occurrence and development of human tumors.

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    Thymidylate synthase and tumor
    Huang Zhiguo, Hu Kongwang
    2020, 47 (10):  615-618.  doi: 10.3760/cma.j.cn371439-20200318-00088
    Abstract ( 645 )   HTML ( 26 )   PDF (660KB) ( 304 )   Save

    Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is often used as a target for chemotherapy drugs. In a variety of tumors such as non-small cell lung cancer, colorectal cancer, breast cancer, etc, the expression of TS is closely related to the clinical prognosis and chemotherapy drug resistance of patients. Reducing the expression of TS in tumor tissues through various molecular mechanisms has become an important means to improve the efficacy of chemotherapy drugs and improve the clinical prognosis.

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    New progress in antitumor research of non-psychoactive cannabidiol
    Wang Shuang, Tang Yunyun, Yue Qi
    2020, 47 (10):  619-623.  doi: 10.3760/cma.j.cn371439-20200615-00089
    Abstract ( 474 )   HTML ( 31 )   PDF (667KB) ( 351 )   Save

    Cannabidiol is one of the most abundant phytocannabinoids in hemp, which has no psychoactive properties and a variety of pharmacological actions in vivo. Several recent studies indicate that cannabidiol possesses antitumor activity, the diversity of its acting receptor distribution and activation mechanism makes it possible to inhibit tumorigenesis in multiple ways via affecting tumor cell proliferation, inducing apoptosis, inhibiting cell invasion and metastasis, anti-angiogenesis and regulating immune response. Further understanding of the mechanism of cannabidiol in tumors may provide new ideas for the development of new antitumor agents.

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    Mechanisms of microrobot in cancer therapy
    Zhang Baihong, Yue Hongyun
    2020, 47 (10):  624-626.  doi: 10.3760/cma.j.cn371439-20191016-00090
    Abstract ( 452 )   HTML ( 29 )   PDF (646KB) ( 341 )   Save

    Microrobots (from several millimetres down to a few micrometres in all dimensions) are constructed of nanoscale or molecular components and include various types of magneto-aerotactic bacteria microrobots, nanomotors, biohybrid magnetite microrobots, DNA nanorobots, soft-bodied robots and soft matter. Microrobots may enable applications in cargo delivery, targeting cancer, cellular manipulation and killing cancer. Microrobots swarms exhibit a variety of intriguing collective behaviors, and will serve as a functional bio-microrobot system for cancer "subtle therapy".

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    Research progress of immune-related pneumonia caused by PD-1/PD-L1 inhibitor
    Song Bo, Wu Mingxin, Jia Yingjie, Li Xiaojiang
    2020, 47 (10):  627-629.  doi: 10.3760/cma.j.cn371439-20200609-00091
    Abstract ( 1353 )   HTML ( 64 )   PDF (650KB) ( 489 )   Save

    The incidence of immune-related pneumonia caused by programmed death-1/programmed death ligand-1 inhibitors is low, but the risk is high. Patients with non-small cell lung cancer who have pre-existing lung diseases or have received chest radiotherapy are more likely to develop pneumonia, but their clinical symptoms are not typical, which reduces the survival benefit of patients. Delaying immunotherapy early and rationally using glucocorticoids and immunosuppressants can relieve clinical symptoms and improve prognosis.

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    Research progress of stereotactic body radiation therapy for lung oligometastases of colorectal cancer
    Zhang Lili, Yu Yonghua
    2020, 47 (10):  630-633.  doi: 10.3760/cma.j.cn371439-20200306-00092
    Abstract ( 1031 )   HTML ( 31 )   PDF (661KB) ( 382 )   Save

    Compared with surgery and radiofrequency ablation, stereotactic body radiation therapy (SBRT) has similar efficacy for local treatment of colorectal cancer with pulmonary oligometastasis, but it applies to a wide range of people. Oligometastasis of colorectal cancer may have radiation resistance, and good local control can be achieved by increasing the dose. The prescription dose and prognostic factors of SBRT in the treatment of lung oligometastasis of colorectal cancer have not been determined. There are no serious toxicities in most studies, but there are still radiation-related adverse events.

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    Application of exosomes in prostates cancer
    Zhang Jiawei, Wu Jianchen
    2020, 47 (10):  634-636.  doi: 10.3760/cma.j.cn371439-20200401-00093
    Abstract ( 630 )   HTML ( 28 )   PDF (649KB) ( 239 )   Save

    Exosomes derived from prostate cancer cells can directly or indirectly promote the growth and metastasis of prostate cancer cells. It was found that it can be used as a marker for diagnosis and prognosis evaluation of prostate cancer, and participate in the clinical treatment of prostate cancer, such as targeted therapy, drug resistance assessment, tumor vaccine preparation, etc. With the development of various studies and technological progress, exosomes will play a huge role in the diagnosis and treatment of prostate cancer.

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    Prognostic role and mechanisms of abnormal coagulation system in lymphoma
    Chai Yue, Dong Mei
    2020, 47 (10):  637-640.  doi: 10.3760/cma.j.cn371439-20200318-00094
    Abstract ( 1189 )   HTML ( 33 )   PDF (662KB) ( 344 )   Save

    Lymphoma is the most common hematological malignancy, often accompanied by coagulation abnormalities. Coagulative dysfunction leads to thromboembolic and bleeding complications, which greatly increases mortality in patients with lymphoma. The mechanisms of abnormal coagulation system in lymphoma mainly include the direct coagulation mechanism of tumor cells secreting procoagulant factors and the indirect coagulation mechanism of tumor cells activating the procoagulant potential of host cells. Coagulative factors may be related to the prognosis of lymphoma.

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