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Table of Content

28 June 2022, Volume 36 Issue 3
Cancer Screening
Comparative study on application effect of two risk assessment models in screening colorectal cancer
LI Bo, PENG Xiaolin, WANG Shanshan, LI Gairui, ZHAO Dan, PENG Ji
2022, 36(3):  197-202.  doi:10.11904/j.issn.1002-3070.2022.03.001
Abstract ( 126 )   PDF (12760KB) ( 53 )  
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Objective The aim of this study was to compare the application effects of two risk assessment models in the early screening of colorectal cancer,and to explore an evaluation model that was more suitable for the early screening of colorectal cancer in Chinese residents. Methods The 40-74 years old permanent residents who participated in the urban cancer early diagnosis and early treatment project in Nanshan District,Shenzhen from 2017 to 2019 were selected as the research subjects.Two risk assessment models were used to assess the risk of colorectal cancer in the same population and compare the screening performance and predicted value. Results A total of 4 141 participants were included,with an average age of 56.4±9.0 years old.The positive rates of model 1 and model 2 were 15.2% and 21.3%,respectively,and the overall agreement rate was 93.50%(Kappa value=0.784,P<0.001).Among 702 colonoscopy examiners,the detection rates of enteritis,polyps,adenomas,CRC,and other intestinal lesions were 12.5%,12.0%,15.8%,0.7%,and 30.7%,respectively.There was no statistically significant difference in the distribution of colonoscopy results(χ2=8.679,P=0.123).The sensitivity of model 1 was 45.7%,which was lower than that of model 2(61.2%);while the specificity(64.8%),positive predictive value(76.7%),Kappa value(0.081)and Youden index(0.103)were higher than those in model 2(41.7%,72.6%,0.026 and 0.029).The areas under the ROC curves for the two models were 0.660(95% CI:0.618-0.702)and 0.675(95%CI:0.634-0.715),respectively,and there was no significant difference(P=0.584). Conclusion Both RAMs have certain predictive power and advantages for early diagnosis of CRC,but model 1 is slightly better than model 2 in terms of screening accuracy and screening benefit.In large-scale population screening,it is recommended the two models learn from each other′s strengths and complement their weaknesses,and are comprehensively applied.
Basic Research
Aqueous Huaier extract inhibits the proliferation and metastasis of hepatocellular carcinoma by regulating the Akt signaling pathway through mitochondrial transcription factor A
LIU Jiaming, CUI Yifeng, LU Zhaoyang
2022, 36(3):  203-207.  doi:10.11904/j.issn.1002-3070.2022.03.002
Abstract ( 113 )   PDF (11231KB) ( 29 )  
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Objective The aim of this study was to study the effect of aqueous Huaier extract on hepatocellular carcinoma and explore its potential molecular mechanism. Methods HCCLM3 cells were stimulated by different concentrations of aqueous Huaier extract as the treatment group,and untreated HCCLM3 cells as the control group.Cell viability was detected by CCK-8,cell proliferation was detected by colony formation assay,and cell metastasis was detected by Transwell assay.The expression changes of message RNA(mRNA)of HCCLM3 cells in the treatment group and control group were detected by high-throughput sequencing.The mitochondrial transcription factor A(TFAM)with obvious fold changes was selected as the research object.The results of microarray sequencing were detected by polymerase chain reaction and Western blot. Results The results of the CCK-8 experiment showed that from the third day, the Huaier 6 mg/mL group inhibited cell viability significantly stronger than the Huaier 3 mg/mL group and the control group(P<0.05);The results showed that the number of cell clones in the Huaier 6 mg/mL group was significantly higher than that in the Huaier 3 mg/mL group and the control group(55.67±5.03 vs. 48.33±4.04 vs. 37.33±2.52,P<0.05);Transwell test results showed that the metastatic ability of Huaier 6 mg/mL group was significantly stronger than that of Huaier 3 mg/mL group and control group(67.00±4.58 vs. 44.00±3.00 vs. 22.33±2.52,P<0.01);high-throughput sequencing results found 486 differentially expressed genes(fold change>2,P<0.05),of which 317 genes were up-regulated and 115 genes were down-regulated in the experimental group.PCR experiments And Western blot experiments confirmed that Huaier can significantly reduce the expression of TFAM in liver cancer cells(1.00±0.04 vs. 0.45±0.16,P<0.01).After Huaier stimulated HCCLM3 cells, the protein expression of p-Akt was significantly decreased, while the total AKT content did not change. Conclusion Aqueous Huaier extract can effectively inhibit the proliferation and metastasis of HCC,and this effect may be achieved by reducing the expression of TFAM and thereby inhibiting the activation of Akt signaling pathway.
Mechanism of lncRNA-ATB mediated epithelial mesenchymal transition in the progression of gastric cancer
ZHI Lianghui, LIU Wei, LI Wei, ZHEN Sihu, JIAO Xilin
2022, 36(3):  208-213.  doi:10.11904/j.issn.1002-3070.2022.03.003
Abstract ( 78 )   PDF (12118KB) ( 25 )  
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Objective The objective of this study was to investigate the possible mechanism of lncRNA-ATB mediated epithelial-mesenchymal transition(EMT)in the progression of gastric cancer. Methods The downstream binding molecules of lncRNA-ATB were predicted by bioinformatics analysis and verified by luciferase reporter gene.A total of 56 gastric cancer and adjacent tissue specimens from the 980th Hospital of the Joint Logistics Support Force were collected from January 2017 to December 2019.The levels of lncRNA-ATB and the downstream binding molecules in gastric cancer and adjacent tissues as well as their relationship were analyzed by qRT-PCR.Its correlation with clinicopathological features of gastric cancer was also analyzed.The expression of miR-200a,β-catenin,vimentin and E-cadherin was confirmed by qRT-PCR and Western blot in gastric cancer BGC-823 cells before and after knockdown of lncRNA-ATB. Results Bioinformatics analysis showed that lncRNA-ATB had a direct binding site to miR-200a,and miR-200a could directly bind to β-catenin,which was verified by luciferase reporter gene.The expression of lncRNA-ATB in gastric cancer tissues was significantly higher than that in adjacent tissues(P<0.001),and the expression of miR-200a in gastric cancer was significantly lower than that in adjacent tissues,the difference was statistically significant(P<0.001).There was a negative correlation between the levels of lncRNA-ATB and miR-200a in gastric cancer tissues(r=-0.317,P=0.017).The expression of lncRNA-ATB in the stage III and IV gastric cancer was significantly higher than that in the stage I and II gastric cancer,and the expression of lncRNA-ATB in patients with the lymph node metastasis positive group,vascular tumor thrombus positive group and tumor poorly differentiated group was significantly higher than that in the negative group,and the difference was statistically significant(P<0.001).The expression of miR-200a in the stage III and IV gastric cancer patients was significantly lower than that in the stage I and II patients,and the expression of miR-200a in patients with the lymph node metastasis positive group,vascular tumor thrombus positive group and tumor poorly differentiated group was significantly lower than that in the negative group,and the difference was statistically significant(P<0.05).After knockdown of lncRNA-ATB in BGC-823 cells,the expression of β-catenin and vimentin was decreased and the expression of E-cadherin was increased,and the differences were statistically significant(P<0.05). Conclusion lncRNA-ATB can affect the progression of gastric cancer by binding to miR-200a,affecting the expression of β-catenin and promoting the process of EMT.
Clinical Research
Analysis of the correlation between sarcopenia and the clinicopathological characteristics and prognosis of advanced NSCLC
ZHANG Hao, YANG Xinguan, HE Yong
2022, 36(3):  214-219.  doi:10.11904/j.issn.1002-3070.2022.03.004
Abstract ( 112 )   PDF (11637KB) ( 24 )  
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Objective The objective of this study was to determine the clinicopathological characteristics of advanced non-small cell lung cancer patients with sarcopenia,and to evaluate the effect of sarcopenia on progression-free survival(PFS)and overall survival(OS)in advanced non-small cell lung cancer patients. Methods A total of 112 patients with stage IIIb-IV non-small cell lung cancer who were treated in our hospital from June 2017 to December 2019 were selected,and the patients were divided into the sarcopenia group(64 cases)and the non-sarcopenia group(48 cases).All patients were followed up by telephone or outpatient service.PFS and OS between the two groups were compared.Cox regression was used to analyze the prognostic risk factors of advanced non-small cell lung cancer. Results The survival rates of PFS and OS in the group with sarcopenia were lower than those in the group without sarcopenia(P<0.05).Multivariate Cox hazard proportional regression analysis showed that sarcopenia and T stage were independent risk factors for PFS in patients with advanced non-small cell lung cancer(P<0.05);sarcopenia and lymph node metastasis were independent risk factors for OS in patients with advanced non-small cell lung cancer(P<0.05). Conclusion The PFS and OS of advanced non-small cell lung cancer patients with sarcopenia are lower than those of non-sarcopenic patients,sarcopenia may be used as a prognostic indicator for advanced non-small cell lung cancer patients.
Analysis of 131I efficacy prediction model for non-distant metastatic papillary thyroid carcinoma
LIANG Jie, WANG Xinhua, WANG Jian, XIA Huan
2022, 36(3):  220-225.  doi:10.11904/j.issn.1002-3070.2022.03.005
Abstract ( 98 )   PDF (12108KB) ( 30 )  
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Objective The objective of this study was to analyze the risk factors affecting the curative effect of 131I treatment for non-distant metastatic papillary thyroid carcinoma(PTC),and construct a predictive model for curative effect. Methods The clinical data of 422 patients who underwent thyroid cancer resection and 131I treatment in our hospital from January 2016 to December 2020 were retrospectively analyzed.Multivariate logistic regression analysis was used to screen independent risk factors affecting the efficacy of 131I treatment,and the efficacy predictive model was constructed as well as its evaluation and validation. Results Selecting 75% patients as training set(n=319),25% patients as validation set(n=103).After multivariate logistic regression analysis in the training set,the independent risk factors of unsatisfactory 131I treatment for non-distant metastatic PTC were positive BRAFV600E mutation,sTg/TSH≥0.05 ng/μIU,sTg/TgAb≥0.60 ng/IU,the largest diameter of lesions≥1.05 cm,the lymph node staging N1b and the lymphatic metastasis rate≥34.58%(P<0.05).A nomogram model was constructed,and the areas under the ROC curve in the training set and validation set were 0.90(95% CI:0.87-0.94,P<0.001)and 0.86(95% CI:0.78-0.94,P<0.001),respectively. Conclusion The efficacy predictive model constructed in this study based on the risk factors of unsatisfactory 131I treatment efficacy in non-distant metastatic PTC has good predictive performance.
Characteristics of breast cancer metastases to outer triangle tissue and its influencing factors
YANG Zihan, XU Shouping, PANG Da
2022, 36(3):  226-232.  doi:10.11904/j.issn.1002-3070.2022.03.006
Abstract ( 175 )   PDF (13470KB) ( 24 )  
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Objective The aims of this study were to evaluate the risk factors of outer triangle tissue metastases,screen the patients with few outer triangle tissue metastases and discuss the significance of outer triangle tissue preservation. Methods A total of 150 patients underwent axillary lymph node dissection(ALND)in Harbin Medical University Cancer Hospital from September 2020 to June 2021 was conducted for this retrospective study.Patients were divided into two groups according to neoadjuvant therapy(NAC),with 95 patients in none NAC group and 55 patients in NAC group.The correlation between clinical data and outer triangle tissue metastases was analyzed.Multivariate logistic regression analysis was used to screen the risk factors and ROC curve was used to evaluate the combined diagnosis. Results In total sample,22 patients were detected outer triangle tissue metastases.Among 95 none NAC patients,19 patients(20%)had outer triangle tissue metastases.The size of lymph node in ultrasound was correlated with outer triangle tissue metastases(P=0.011).Multivariate logistic analysis showed that age ≤55 years,lymph node size and progesterone receptor condition were independent influencing factors for outer triangle tissue metastases.According to ROC analysis,the area under the curve was 0.820,specificity was 77.8%,sensitivity was 78.7%.Among 55 NAC patients,3 patients(5.5%)were detected outer triangle tissue metastases. Conclusion Lymph node size and pN stage are the influencing factors for outer triangle tissue metastases.Patients with NAC can be exempted from outer triangle tissue dissection.
FSIP1 promotes migration and invasion of breast cancer cells and leads to poor prognosis of patients
HE Weidan, LI Zhigao
2022, 36(3):  233-238.  doi:10.11904/j.issn.1002-3070.2022.03.007
Abstract ( 102 )   PDF (12915KB) ( 28 )  
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Objective The aims of this study were to investigate the effect of FSIP1 expression in breast cancer tissues on the migration and invasion ability of breast cancer cells,and its relationship with the prognosis of breast cancer patients,so as to provide certain theoretical reference for the diagnosis and treatment of breast cancer. Methods The breast tissue samples and case data of 404 breast cancer patients diagnosed in Harbin Medical University Cancer Hospital from January 2004 to December 2018 were collected.The collected data of breast cancer patients were retrospectively analyzed and the survival curve was plotted by Kaplan-Meier method.Immunohistochemistry was used to analyze the expression of FSIP1 in breast cancer and adjacent tissues,and breast cancer MCF-7,MDA-MB-231,MDA-MB-435,SK-BR-3,T-47D and HMECs(MCF-10A)cell lines were cultured.The FSIP1 gene in breast cancer MDA-MB-231 and SK-BR-3 cell lines was knocked out using CRISPR/CAS9 technology and detected by Western blot.The effect of FSIP1 gene knockout on migration and invasion abilities of breast cancer cells was evaluated through cell migration and invasion assays. Results Compared with HMECs(MCF-10A),the expression of FSIP1 in breast cancer MCF-7,MDA-MB-231,MDA-MB-435,SK-BR-3,and T-47D cell lines was significantly increased(P<0.01).Compared with adjacent breast tissues,the expression of FSIP1 in breast cancer tissues was significantly increased(P<0.01).Survival analysis showed that the overall survival of breast cancer patients with the high expression of FSIP1 was significantly shortened(P<0.01).The expression of FSIP1 was correlated with the clinical stage of breast cancer(P=0.0061)and the expression of cell proliferation marker-Ki-67(P=0.0067).The results of migration and invasion experiments showed that after knocking out the FSIP1 gene,the migration and invasion capabilities of breast cancer MDA-MB-231 and SK-BR-3 cells were significantly reduced(P<0.01). Conclusion The high expression of FSIP1 in breast cancer cells can enhance their migration and invasion capabilities,and is correlated with the poor prognosis of patients.
Review
Research progress in molecular mechanism of liver cancer comorbid and depression
TANG Rubing, WANG Qi, YOU Xuemei
2022, 36(3):  239-244.  doi:10.11904/j.issn.1002-3070.2022.03.008
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The incidence of comorbid depression in patients with liver cancer is extremely high.The depression is an adverse factor affecting the prognosis of liver cancer patients.Understanding the molecular mechanism of liver cancer comorbid and depression is crucial for the diagnosis and treatment of the disease.Therefore,this paper reviews the pathogenesis involved in both as a starting point and combines the existing research results from autonomic dysfunction,hypothalamic-pituitary-adrenal(HPA)axis dysfunction,inflammatory cytokines imbalance,abnormal regulation of 5-hydroxytryptamine(5-HT)system,imbalance of intestinal flora,and oxidative stress are reviewed.
Research progress in the inhibitory effects of plant anthocyanins on tumors
YU Xiaolan, LIU Yan, LIU Jiaren
2022, 36(3):  245-249.  doi:10.11904/j.issn.1002-3070.2022.03.009
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Plant anthocyanins are a class of water-soluble flavonoids,which mainly found in various vegetables and fruits.Common plant anthocyanins are mainly divided into six species including pelargonidin,peonidin,cyanidin,malvidin,petunidin,and delphinidin;Because the phytocyanin molecules contain conjugated double bond systems with basic or acidic groups,they have biological effects such as anti-oxidation,anti-inflammation,immune regulation,anti-aging,and anti-cancer,especially for inhibitory effects of tumor.Therefore,this article will review tumor suppressive effects and possible mechanisms of plant anthocyanins.
Research progress in the role of chemokine CCL20 in breast cancer microenvironment
LIU Xinxin, YAO Xinhui, SUN Yuefeng, MIU Meiqi, CHEN Jing
2022, 36(3):  250-254.  doi:10.11904/j.issn.1002-3070.2022.03.010
Abstract ( 100 )   PDF (11847KB) ( 19 )  
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Chemokines are a class of low molecular weight cytokines,which play an important role in regulating the tumor microenvironment.Chemokines in the tumor microenvironment can not only trend chemotactic leukocytes,but also induce nearby respond cells to affect tumor growth,invasion,metastasis and angiogenesis.Chemokines are closely related to the occurrence and development of inflammation diseases and tumors.Among them,chemokine CCL20 in the CC family plays an important role in the invasion and metastasis of various malignant tumors.In recent years,it has been found that the chemokine CCL20 plays an important regulatory role in breast cancer immunosuppression,angiogenesis,induction of epithelial-mesenchymal transition,tumor invasion and metastasis.However,the mechanism of CCL20 action in breast cancer is not fully understood.This article focuses on the function of CCL20,a member of the chemokine CC subfamily,in the breast cancer microenvironment,and discusses the relationship between CCL20 and the breast cancer microenvironment,in order to provide new ideas for breast cancer targeted therapy.
Research progress of eccDNA in cancer
YU Chengping, CUI Yongkang, LI Linqiang
2022, 36(3):  255-258.  doi:10.11904/j.issn.1002-3070.2022.03.011
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The DNA of eukaryotic cells mainly exists on the chromosomes,but in fact there is also DNA outside chromosomes,which is a special kind of circular DNA(extrachromosomal circular DNA,eccDNA).Several types of eccDNA have been discovered,including small polydispersed DNA(spcDNA),telomere loops,extrasomal rDNA loops and microDNA(miDNA),etc.eccDNA is separated or detached from the genome,coexists with the chromosomal DNA,and participates in pathological or physiological processes of the body in a special way.This paper summarizes the classification,formation mechanism,expression and role formation of eccDNA in cancer.
Research progress of DNA methylation in diffuse large B-cell lymphoma
ZHENG Yanli, HE Jianxia
2022, 36(3):  259-262.  doi:10.11904/j.issn.1002-3070.2022.03.012
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Diffuse large B-cell lymphoma(DLBCL)is a common type of adult lymphoma with high heterogeneity and different clinical and pathological features.Although some DLBCLs are curable,the management of refractory and relapsed patients remains challenging.In recent years,epigenetic modifications such as DNA methylation have become a research hotspot of DLBCL.Gene mutations regulating methylation modification and methylation modification of tumor suppressor genes play a key role in the pathogenesis and prognosis of DLBCL.This paper reviews the research progress of DNA methylation in DLBCL.
Research status and application prospect of UCA1 in breast cancer
YANG Shuya, LIU Wenhui, LUO Naixiang
2022, 36(3):  263-267.  doi:10.11904/j.issn.1002-3070.2022.03.013
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Breast cancer is the most common malignant tumor in women worldwide,and its occurrence and development are related to various factors such as heredity,environment,and hormone levels.Recent studies have found that long non-coding RNAs(lncRNAs)play an important role in the occurrence and development of breast cancer.The urothelial cancer-associated 1(UCA1)gene is a kind of lncRNA,which was first discovered and named in bladder cancer,and its expression was up-regulated in various malignant tumors such as gastric cancer,colorectal cancer,malignant melanoma,and ovarian cancer.This article reviews the relevant roles and mechanisms of UCA1 in breast cancer.It aims to understand the role of UCA1 in the occurrence and development of breast cancer,to provide new indicators and new therapeutic targets for the prevention,diagnosis and recurrence of breast cancer.
Research progress on the mechanism of metastasis in invasive micropapillary carcinoma of the breast
LIU Wanying, PANG Da
2022, 36(3):  268-272.  doi:10.11904/j.issn.1002-3070.2022.03.014
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Invasive micropapillary carcinoma(IMPC)of breast is a rare histopathological variant of breast cancer,accounting for approximately 3%-8% of all breast cancer.Compared with invasive ductal carcinoma of no special type(IDC-NST),although the incidence of IMPC is low,IMPC shows a tendency of lymphatic invasion and lymph node metastasis.Therefore,understanding its metastasis mechanism is particularly important for intervening in the clinical diagnosis and treatment process.This article aims to review the metastatic mechanism of IMPC and related to clinical evidence,so as to provide new ideas for the treatment of IMPC.
Research progress of SMYD2 in malignant tumors
YANG Nan, WANG Zhao, ZHANG Yu, ZHANG Yunyan
2022, 36(3):  273-277.  doi:10.11904/j.issn.1002-3070.2022.03.015
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Lysine methyltransferase 2(SMYD2)is a kind of special lysine methyltransferase containing SET(Suppressor of variegation,Enhancer of zeste,Trithorax)domain and MYND(Myeloid-nervy-deaf1)domain.Through post-translational modifications of histones and other proteins,SMYD2 plays a key role in epigenetics,body development,and carcinogenesis.In recent years,the role of SMYD2 in malignant tumors has received increasing attention.A number of studies have shown that SMYD2 plays an important role in the occurrence,development and metastasis of ovarian cancer,breast cancer,colon cancer,renal cell carcinoma and other malignant tumors.This article describes the research progress of SMYD2 in malignant tumors in recent years.
Research progress in PD-1/PD-L1 immune checkpoint inhibitors in glioblastoma multiforme
TONG Manlin, SHANG Ruru, LIU Xiaohong
2022, 36(3):  278-282.  doi:10.11904/j.issn.1002-3070.2022.03.016
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Glioblastoma multiforme(GBM)is one of the most common primary malignant brain tumors.GBM has the characteristics of high invasiveness,high recurrence rate and low survival rate,with a poor prognosis.Programmed cell death receptor 1(PD-1)/programmed cell death ligand 1(PD-L1)as the main immune checkpoint(IC),the formation of immune pathways can trigger negative regulation of immune response and enhance the invasiveness of GBM cells in brain tissue.Research into GBM treatment is ongoing,and immune checkpoint inhibitors(ICIs)have also received considerable attention.ICIs activate antitumor response by inhibiting negative immunoregulatory pathways,providing a new therapeutic approach for GBM.Several clinical studies have focused on the combination of standard therapy(temozolomide,radiotherapy),targeted therapy,and other immunotherapies.This review describes the PD-1/PD-L1 pathways,and summarizes the research progress of PD-1/PD-L1 monotherapy,neoadjuvant therapy and combined chemotherapy,radiotherapy,targeted therapy,hormones,etc.in the treatment of GBM.
Progress in the treatment of T1 high-grade urothelial carcinoma
WANG Leilei, CHEN Hui
2022, 36(3):  283-287.  doi:10.11904/j.issn.1002-3070.2022.03.017
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Bladder cancer is a common tumor of the urinary system.More than 90% of bladder cancers are urothelial carcinoma.According to the depth of tumor invasion,it can be divided into non-muscle invasive urothelial carcinoma(NMIBC)and muscular invasive urothelial carcinoma.NMIBC has a good prognosis,which mainly refers to tumor invasion into lamina propria(T1),mucosal layer(Ta)and carcinoma in situ(Tis).Among them,Ta and T1 stage tumors account for the majority.Although both belong to NMIBC,their biological characteristics are different from each other.Because of the abundance of blood vessels and lymphatic vessels in lamina propria,T1 stage tumors are more prone to spread and recurrence.This article will focus on different treatment methods for T1 high-grade urothelial carcinoma,including surgical treatment,interventional therapy,drug chemotherapy,immunotherapy,etc.,and especially discusses how to use surgical treatment and surgical treatment combined with chemotherapy to improve the treatment effect,reduce recurrence and improve the survival time.
Research progress of anti-HER2 therapy in metastatic colorectal cancer
CHEN Su, SUI Hong
2022, 36(3):  288-292.  doi:10.11904/j.issn.1002-3070.2022.03.018
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Colorectal cancer(CRC)is the third most common cancer and the second largest cause of cancer-related deaths in the world,which seriously threatens human life and health.Despite early diagnosis and treatment,a considerable number of CRC patients have a poor prognosis due to metastasis.Research on the molecular diversity of CRC not only guides the prognosis,but it also has an important reference significance for the individualized treatment of patients.Human epidermal growth factor receptor-2(HER2)is expressed in breast cancer,gastric cancer and other malignant tumors.Anti-HER2 treatment can effectively improve the prognosis of patients with HER2-positive advanced breast cancer and gastric cancer.HER2,as an emerging biomarker of metastatic colorectal cancer(mCRC),has also attracted much attention in recent years.This article reviews the current research progress in the diagnosis and treatment of HER2-positive mCRC,with a view to providing references for clinical diagnosis and drug selection.